{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T17:03:57Z","timestamp":1779815037521,"version":"3.53.1"},"reference-count":150,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research Project of Traditional Chinese Medicine of Tianjin Municipal Health Commission","award":["2025001"],"award-info":[{"award-number":["2025001"]}]},{"name":"Special Project for Technological Innovation in New Productivie Forces of Modern Chinese Medicines","award":["24ZXZKSY00020"],"award-info":[{"award-number":["24ZXZKSY00020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, with renal fibrosis as its core pathological hallmark. A central driver of this fibrosis is epithelial\u2013mesenchymal transition (EMT), during which renal tubular epithelial cells transform into matrix-producing myofibroblasts. Endothelial\u2013mesenchymal transition (EndMT) has also emerged as a critical contributor, and together with EMT, accounts for the progressive accumulation of myofibroblasts and extracellular matrix. A major clinical challenge in halting DKD progression is \u201cmetabolic memory\u201d, a phenomenon whereby renal injury persists and EMT\/EndMT remain activated even after glycemic control is achieved. The molecular basis underlying this sustained activation remains incompletely understood. Emerging evidence indicates that metabolic memory is largely mediated by epigenetic mechanisms, including histone modifications, DNA methylation, and non-coding RNA dysregulation. These stable epigenetic imprints maintain the persistent activation of key pro-fibrotic signaling pathways, especially TGF-\u03b2, thereby continuously driving EMT, EndMT, and excessive extracellular matrix deposition. Although targeting epigenetic regulators has shown promising anti-fibrotic effects, a systematic review that integrates how metabolic memory orchestrates both EMT and EndMT through a multi-layered epigenetic network remains lacking. This review comprehensively summarizes the epigenetic mechanisms by which metabolic memory sustains EMT and EndMT in DKD, highlights key therapeutic targets, and discusses their translational and clinical implications.<\/jats:p>","DOI":"10.3390\/ijms27114801","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T16:17:58Z","timestamp":1779812278000},"page":"4801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Memory-Mediated Epigenetic Regulation of EMT in Diabetic Kidney Disease: Mechanisms and Therapeutic Implications"],"prefix":"10.3390","volume":"27","author":[{"given":"Xinning","family":"Ran","sequence":"first","affiliation":[{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidan","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruonan","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Duan","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"Jia","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Bian","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenduo","family":"Li","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Scilletta, S., Maurizio, D.M., Nicoletta, M., Agnese, F., Stefania, D.M., Alessandra, S., Marco, M., Giuseppe, C., Francesco, D.G., and Giosiana, B. (2023). Update on Diabetic Kidney Disease (DKD): Focus on Non-Albuminuric DKD and Cardiovascular Risk. Biomolecules, 13.","DOI":"10.3390\/biom13050752"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sagoo, M.K., and Gnudi, L. (2020). Diabetic Nephropathy: An Overview, Springer.","DOI":"10.1007\/978-1-4939-9841-8_1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0344-0338(11)81021-6","article-title":"The consequences of tubulo-interstitial changes for renal function in glomerulopathies. A morphometric and cytological analysis","volume":"186","author":"Bohle","year":"1990","journal-title":"Pathol. Res. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15018","DOI":"10.1038\/nrdp.2015.18","article-title":"Diabetic kidney disease","volume":"1","author":"Thomas","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2858","DOI":"10.2174\/0929867322666150625095407","article-title":"Insights into the Mechanisms Involved in the Expression and Regulation of Extracellular Matrix Proteins in Diabetic Nephropathy","volume":"22","author":"Hu","year":"2015","journal-title":"Curr. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1046\/j.1523-1755.2000.00868.x","article-title":"Expression of decorin, biglycan, and collagen type I in human renal fibrosing disease","volume":"57","author":"Stokes","year":"2000","journal-title":"Kidney Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/s41581-025-00934-5","article-title":"Advances and challenges in kidney fibrosis therapeutics","volume":"21","author":"Abbad","year":"2025","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nrm3758","article-title":"Molecular mechanisms of epithelial\u2013mesenchymal transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1146\/annurev-physiol-022516-034227","article-title":"Mechanisms of Renal Fibrosis","volume":"80","author":"Humphreys","year":"2018","journal-title":"Annu. Rev. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chatterjee, A., Tumarin, J., and Prabhakar, S. (2025). Cellular cross-talk drives mesenchymal transdifferentiation in diabetic kidney disease. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1499473"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"553","DOI":"10.2337\/cd22-0110","article-title":"Perspectives on Chronic Kidney Disease With Type 2 Diabetes and Risk Management: Practical Viewpoints and a Paradigm Shift Using a Pillar Approach","volume":"41","author":"Morales","year":"2023","journal-title":"Clin. Diabetes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2337\/dc13-2113","article-title":"Kidney Disease and Related Findings in the Diabetes Control and Complications Trial\/Epidemiology of Diabetes Interventions and Complications Study","volume":"37","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"F327","DOI":"10.1152\/ajprenal.00115.2024","article-title":"Update: The role of epigenetics in the metabolic memory of diabetic complications","volume":"327","author":"Chen","year":"2024","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev.pathol.4.110807.092150","article-title":"A Glimpse of Various Pathogenetic Mechanisms of Diabetic Nephropathy","volume":"6","author":"Kanwar","year":"2011","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1755-5922.2010.00218.x","article-title":"Relationship between Oxidative Stress and Inflammatory Cytokines in Diabetic Nephropathy","volume":"30","author":"Elmarakby","year":"2012","journal-title":"Cardiovasc. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"181","DOI":"10.4093\/dmj.2021.0329","article-title":"Pathophysiologic Mechanisms and Potential Biomarkers in Diabetic Kidney Disease","volume":"46","author":"Jung","year":"2022","journal-title":"Diabetes Metab. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1017\/S1462399409001057","article-title":"Transcription factors in the pathogenesis of diabetic nephropathy","volume":"11","author":"Sanchez","year":"2009","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1042\/CS20120198","article-title":"Inflammation and the pathogenesis of diabetic nephropathy","volume":"124","author":"Wada","year":"2013","journal-title":"Clin. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1097\/01.ASN.0000093460.24823.5B","article-title":"Mediators of diabetic renal disease: The case for TGF-\u03b2 as the major mediator","volume":"15","author":"Ziyadeh","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.tibs.2004.03.008","article-title":"New insights into TGF-\u03b2\u2013Smad signalling","volume":"29","author":"Dijke","year":"2004","journal-title":"Trends Biochem. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1053\/S0270-9295(03)00132-3","article-title":"Diabetic nephropathy and transforming growth factor-\u03b2: Transforming our view of glomerulosclerosis and fibrosis build-up","volume":"23","author":"Chen","year":"2003","journal-title":"Semin. Nephrol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.matbio.2018.02.006","article-title":"Renal fibrosis: Primacy of the proximal tubule","volume":"68\u201369","author":"Gewin","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1172\/JCI0215518","article-title":"Evidence that fibroblasts derive from epithelium during tissue fibrosis","volume":"110","author":"Iwano","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1159\/000541923","article-title":"Role of Epigenetic Changes in the Pathophysiology of Diabetic Kidney Disease","volume":"4","author":"Liebisch","year":"2024","journal-title":"Glomerular Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1097\/00041552-200111000-00001","article-title":"Pathogenesis of diabetic nephropathy: Focus on transforming growth factor-\u03b2 and connective tissue growth factor","volume":"10","author":"Sakharova","year":"2001","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"20130363","DOI":"10.1098\/rsif.2013.0363","article-title":"Computational modelling of Smad-mediated negative feedback and crosstalk in the TGF-\u03b2 superfamily network","volume":"10","author":"Nicklas","year":"2013","journal-title":"J. R. Soc. Interface"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.biocel.2012.01.021","article-title":"Notch signaling mediates TGF-\u03b21-induced epithelial\u2013mesenchymal transition through the induction of Snai1","volume":"44","author":"Matsuno","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1101\/gad.1350705","article-title":"Smad transcription factors","volume":"19","author":"Seoane","year":"2005","journal-title":"Genes Dev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1242\/jcs.003129","article-title":"TGF\u03b23 inhibits E-cadherin gene expression in palate medial-edge epithelial cells through a Smad2-Smad4-LEF1 transcription complex","volume":"120","author":"Nawshad","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1083\/jcb.200306024","article-title":"TGF\u03b23 signaling activates transcription of the LEF1 gene to induce epithelial mesenchymal transformation during mouse palate development","volume":"163","author":"Nawshad","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13020-017-0134-0","article-title":"Jiangtang decoction ameliorate diabetic nephropathy through the regulation of PI3K\/Akt-mediated NF-\u03baB pathways in KK-Ay mice","volume":"12","author":"Hong","year":"2017","journal-title":"Chin. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s00441-011-1201-y","article-title":"Non-Smad signaling pathways","volume":"347","author":"Mu","year":"2012","journal-title":"Cell Tissue Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"463740","DOI":"10.1155\/2013\/463740","article-title":"Both ERK\/MAPK and TGF-Beta\/Smad Signaling Pathways Play a Role in the Kidney Fibrosis of Diabetic Mice Accelerated by Blood Glucose Fluctuation","volume":"2013","author":"Cheng","year":"2013","journal-title":"J. Diabetes Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"116768","DOI":"10.1016\/j.jep.2023.116768","article-title":"Liensinine improves AngII-induced vascular remodeling via MAPK\/TGF-\u03b21\/Smad2\/3 signaling","volume":"317","author":"Jia","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/s41419-022-04609-y","article-title":"Numb-PRRL promotes TGF-\u03b21- and EGF-induced epithelial-to-mesenchymal transition in pancreatic cancer","volume":"13","author":"Sheng","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1080\/01635581.2014.853087","article-title":"Saponins from the Roots of Platycodon grandiflorum Suppresses TGF\u03b21-Induced Epithelial-Mesenchymal Transition Via Repression of PI3K\/Akt, ERK1\/2 and Smad2\/3 Pathway in Human Lung Carcinoma A549 Cells","volume":"66","author":"Choi","year":"2013","journal-title":"Nutr. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"36803","DOI":"10.1074\/jbc.M005912200","article-title":"Phosphatidylinositol 3-Kinase Function Is Required for Transforming Growth Factor \u03b2-mediated Epithelial to Mesenchymal Transition and Cell Migration","volume":"275","author":"Bakin","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.yexcr.2012.02.036","article-title":"Notch signaling in diabetic nephropathy","volume":"318","author":"Bonegio","year":"2012","journal-title":"Exp. Cell Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"151181","DOI":"10.1016\/j.ejcb.2021.151181","article-title":"ROS-Nrf2 pathway mediates the development of TGF-\u03b21-induced epithelial-mesenchymal transition through the activation of Notch signaling","volume":"100","author":"Yazaki","year":"2021","journal-title":"Eur. J. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/kisup.2014.16","article-title":"Wnt\/\u03b2-catenin signaling and kidney fibrosis","volume":"4","author":"Tan","year":"2014","journal-title":"Kidney Int. Suppl."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.1002\/ctm2.127","article-title":"TGF-\u03b2\/Smad and Wnt\/\u03b2-catenin signaling pathways are involved in renal fibrosis and its therapies","volume":"10","author":"Ying","year":"2020","journal-title":"Clin. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1111\/jcmm.13085","article-title":"Activation of Wnt\/\u03b2-catenin signalling is required for TGF-\u03b2\/Smad2\/3 signalling during myofibroblast proliferation","volume":"21","author":"Xu","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"897","DOI":"10.24272\/j.issn.2095-8137.2022.110","article-title":"The Hippo pathway and its correlation with acute kidney injury","volume":"43","author":"Zhang","year":"2022","journal-title":"Zool. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liu, X., Zhang, C., Fu, Y., Xie, L., Kong, Y., and Yang, X. (2025). Inflammation, Apoptosis, and Fibrosis in Diabetic Nephropathy: Molecular Crosstalk in Proximal Tubular Epithelial Cells and Therapeutic Implications. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47110885"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Yang, Z., He, L.-J., and Sun, S.-R. (2019). Role of Endothelial Cells in Renal Fibrosis, Springer.","DOI":"10.1007\/978-981-13-8871-2_8"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14361","DOI":"10.1038\/ncomms14361","article-title":"The molecular basis of endothelial cell plasticity","volume":"8","author":"Dejana","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1177\/0271678X251388370","article-title":"Spatial transcriptomics reveals TGF-\u03b2-driven endothelial\u2013mesenchymal transition in vascular remodeling of moyamoya disease","volume":"46","author":"Xiao","year":"2026","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Pardali, E., Sanchez-Duffhues, G., Gomez-Puerto, M.C., and Dijke, P.T. (2017). TGF-\u03b2-Induced Endothelial-Mesenchymal Transition in Fibrotic Diseases. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102157"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1161\/CIRCRESAHA.113.300506","article-title":"Regulation of Endothelial Cell Differentiation and Specification","volume":"112","author":"Marcelo","year":"2013","journal-title":"Circ. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"154700","DOI":"10.1016\/j.phymed.2023.154700","article-title":"Rutin alleviates EndMT by restoring autophagy through inhibiting HDAC1 via PI3K\/AKT\/mTOR pathway in diabetic kidney disease","volume":"112","author":"Dong","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1161\/ATVBAHA.124.320933","article-title":"Endothelial TGF-\u03b2 Signaling Regulates Endothelial-Mesenchymal Transition During Arteriovenous Fistula Remodeling in Mice With Chronic Kidney Disease","volume":"44","author":"Zhang","year":"2024","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13072-025-00649-8","article-title":"Research advances in epigenetic modifications and post-translational modifications in endothelial-mesenchymal transition","volume":"18","author":"Shen","year":"2025","journal-title":"Epigenetics Chromatin"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Jun, Q., Youhong, L., Yuan, Z., Xi, Y., Wang, B., Xinyi, S., Fu, Y., Kedan, C., Lian, J., and Jianqing, Z. (2022). Histone modification of endothelial-mesenchymal transition in cardiovascular diseases. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.1022988"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.2337\/diacare.25.8.1410","article-title":"Are Lower Fasting Plasma Glucose Levels at Diagnosis of Type 2 Diabetes Associated with Improved Outcomes?","volume":"25","author":"Colagiuri","year":"2002","journal-title":"Diabetes Care"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"The Writing Team for the Diabetes Control and Complications Trial\/Epidemiology of Diabetes (2003). Sustained Effect of Intensive Treatment of Type 1 Diabetes Mellitus on Development and Progression of Diabetic Nephropathy. JAMA, 290, 2159\u20132167.","DOI":"10.1001\/jama.290.16.2159"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1056\/NEJMoa0806470","article-title":"10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes","volume":"359","author":"Holman","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Diabetes Control and Complications Trial Research Group (1993). The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus. N. Engl. J. Med., 329, 977\u2013986.","DOI":"10.1056\/NEJM199309303291401"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K.B., Ostolaza, H., and Mart\u00edn, C. (2020). Pathophysiology of Type 2 Diabetes Mellitus. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176275"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s00125-014-3462-y","article-title":"Epigenetic mechanisms in diabetic complications and metabolic memory","volume":"58","author":"Reddy","year":"2015","journal-title":"Diabetologia"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13072-018-0251-8","article-title":"Histone H3 lysine K4 methylation and its role in learning and memory","volume":"12","author":"Collins","year":"2019","journal-title":"Epigenetics Chromatin"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Pan, S., Yuan, T., Xia, Y., Yu, W., Zhou, X., and Cheng, F. (2024). Role of Histone Modifications in Kidney Fibrosis. Medicina, 60.","DOI":"10.3390\/medicina60060888"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13148-021-01079-5","article-title":"Effects of metabolic memory on inflammation and fibrosis associated with diabetic kidney disease: An epigenetic perspective","volume":"13","author":"Zheng","year":"2021","journal-title":"Clin. Epigenetics"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41581-019-0135-6","article-title":"Epigenetics and epigenomics in diabetic kidney disease and metabolic memory","volume":"15","author":"Kato","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/ije\/dyr184","article-title":"The Epigenotype","volume":"41","author":"Waddington","year":"2012","journal-title":"Int. J. Epidemiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1868-7083-4-5","article-title":"Roles of histone deacetylases in epigenetic regulation: Emerging paradigms from studies with inhibitors","volume":"4","author":"Delcuve","year":"2012","journal-title":"Clin. Epigenetics"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Martinez-Moreno, J.M., Fontecha-Barriuso, M., Martin-Sanchez, D., Guerrero-Mauvecin, J., Goma-Garces, E., Fernandez-Fernandez, B., Carriazo, S., Sanchez-Ni\u00f1o, M.D., Ramos, A.M., and Ruiz-Ortega, M. (2020). Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114113"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.4161\/epi.21975","article-title":"Histone phosphorylation","volume":"7","author":"Rossetto","year":"2012","journal-title":"Epigenetics"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Cao, J., and Yan, Q. (2012). Histone Ubiquitination and Deubiquitination in Transcription, DNA Damage Response, and Cancer. Front. Oncol., 2.","DOI":"10.3389\/fonc.2012.00026"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e324","DOI":"10.1038\/emm.2017.11","article-title":"Writing, erasing and reading histone lysine methylations","volume":"49","author":"Hyun","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/s41586-019-1678-1","article-title":"Metabolic regulation of gene expression by histone lactylation","volume":"574","author":"Zhang","year":"2019","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1038\/s12276-023-01014-z","article-title":"Histone modifications in drug-resistant cancers: From a cancer stem cell and immune evasion perspective","volume":"55","author":"Jin","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1016\/j.gendis.2022.10.030","article-title":"Epigenetic regulation of mesenchymal stem cell aging through histone modifications","volume":"10","author":"Sun","year":"2023","journal-title":"Genes Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"E127","DOI":"10.1152\/ajpendo.00432.2009","article-title":"Transcriptional coactivator p300 regulates glucose-induced gene expression in endothelial cells","volume":"298","author":"Chen","year":"2010","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.cell.2009.06.049","article-title":"Genome-wide Mapping of HATs and HDACs Reveals Distinct Functions in Active and Inactive Genes","volume":"138","author":"Wang","year":"2009","journal-title":"Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1681\/ASN.2014070678","article-title":"Myocardin-Related Transcription Factor A Epigenetically Regulates Renal Fibrosis in Diabetic Nephropathy","volume":"26","author":"Xu","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41419-020-03322-y","article-title":"Snai1-induced partial epithelial\u2013mesenchymal transition orchestrates p53\u2013p21-mediated G2\/M arrest in the progression of renal fibrosis via NF-\u03baB-mediated inflammation","volume":"12","author":"Qi","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Altalhi, R., Pechlivani, N., and Ajjan, R.A. (2021). PAI-1 in Diabetes: Pathophysiology and Role as a Therapeutic Target. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063170"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1089\/ars.2015.6372","article-title":"Epigenetic Histone Modifications Involved in Profibrotic Gene Regulation by 12\/15-Lipoxygenase and Its Oxidized Lipid Products in Diabetic Nephropathy","volume":"24","author":"Yuan","year":"2016","journal-title":"Antioxid. Redox Signal."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1681\/ASN.2010060633","article-title":"Epigenetic Histone Methylation Modulates Fibrotic Gene Expression","volume":"21","author":"Sun","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/jcb.20532","article-title":"Prospects: Histone deacetylase inhibitors","volume":"96","author":"Dokmanovic","year":"2005","journal-title":"J. Cell. Biochem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"F729","DOI":"10.1152\/ajprenal.00086.2009","article-title":"Histone deacetylase-2 is a key regulator of diabetes- and transforming growth factor-\u03b21-induced renal injury","volume":"297","author":"Noh","year":"2009","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1681\/ASN.2005111187","article-title":"Inhibition of Histone Deacetylase Activity Suppresses Epithelial-to-Mesenchymal Transition Induced by TGF-\u03b21 in Human Renal Epithelial Cells","volume":"18","author":"Yoshikawa","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"909","DOI":"10.4093\/dmj.2020.0168","article-title":"Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7","volume":"45","author":"Kong","year":"2021","journal-title":"Diabetes Metab. J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41419-020-03312-0","article-title":"METTL14-regulated PI3K\/Akt signaling pathway via PTEN affects HDAC5-mediated epithelial\u2013mesenchymal transition of renal tubular cells in diabetic kidney disease","volume":"12","author":"Xu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin Modifications and Their Function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3853242","DOI":"10.1155\/2016\/3853242","article-title":"Involvement of Histone Lysine Methylation in p21 Gene Expression in Rat Kidney In Vivo and Rat Mesangial Cells In Vitro under Diabetic Conditions","volume":"2016","author":"Li","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"12695","DOI":"10.1074\/jbc.RA119.007575","article-title":"Dysregulation of histone H3 lysine 27 trimethylation in transforming growth factor-\u03b21\u2013induced gene expression in mesangial cells and diabetic kidney","volume":"294","author":"Jia","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/s41580-019-0159-6","article-title":"The diverse roles of DNA methylation in mammalian development and disease","volume":"20","author":"Greenberg","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/path.4120","article-title":"The role of promoter hypermethylation in fibroblast activation and fibrogenesis","volume":"229","author":"Zeisberg","year":"2013","journal-title":"J. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/nm.2135","article-title":"Methylation determines fibroblast activation and fibrogenesis in the kidney","volume":"16","author":"Bechtel","year":"2010","journal-title":"Nat. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1681\/ASN.2013070723","article-title":"Tet3-Mediated Hydroxymethylation of Epigenetically Silenced Genes Contributes to Bone Morphogenic Protein 7-Induced Reversal of Kidney Fibrosis","volume":"25","author":"Tampe","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"16338","DOI":"10.1038\/s41598-018-34612-3","article-title":"Aberrant DNA methylation of Tgfb1 in diabetic kidney mesangial cells","volume":"8","author":"Oba","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.bbamcr.2017.03.002","article-title":"TGFbeta-incurred epigenetic aberrations of miRNA and DNA methyltransferase suppress Klotho and potentiate renal fibrosis","volume":"1864","author":"Yin","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s00109-019-01759-z","article-title":"Klotho recovery by genistein via promoter histone acetylation and DNA demethylation mitigates renal fibrosis in mice","volume":"97","author":"Li","year":"2019","journal-title":"J. Mol. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/s41581-022-00608-6","article-title":"MicroRNAs in kidney injury and disease","volume":"18","author":"Mahtal","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.mce.2014.05.018","article-title":"miR-21 overexpression enhances TGF-\u03b21-induced epithelial-to-mesenchymal transition by target smad7 and aggravates renal damage in diabetic nephropathy","volume":"392","author":"Wang","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1042\/CS20150427","article-title":"miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7","volume":"129","author":"McClelland","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"149156","DOI":"10.1016\/j.gene.2024.149156","article-title":"Autocrine small extracellular vesicles induce tubular phenotypic transformation in diabetic nephropathy via miR-21-5p","volume":"938","author":"Zhang","year":"2025","journal-title":"Gene"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.bbrc.2020.10.096","article-title":"miR-30b-5p modulate renal epithelial-mesenchymal transition in diabetic nephropathy by directly targeting SNAI1","volume":"535","author":"Wang","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"37492","DOI":"10.1038\/srep37492","article-title":"The coordinated roles of miR-26a and miR-30c in regulating TGFbeta1-induced epithelial-to-mesenchymal transition in diabetic nephropathy","volume":"6","author":"Zheng","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.semcancer.2020.12.012","article-title":"lncRNA involvement in cancer stem cell function and epithelial-mesenchymal transitions","volume":"75","author":"McCabe","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Wu, Q., and Huang, F. (2023). LncRNA H19: A novel player in the regulation of diabetic kidney disease. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1238981"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.abb.2018.03.018","article-title":"Long non-coding RNA ROR promotes radioresistance in hepatocelluar carcinoma cells by acting as a ceRNA for microRNA-145 to regulate RAD18 expression","volume":"645","author":"Chen","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s13105-019-00688-2","article-title":"lncRNA MALAT1 mediated high glucose-induced HK-2 cell epithelial-to-mesenchymal transition and injury","volume":"75","author":"Zhang","year":"2019","journal-title":"J. Physiol. Biochem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"109411","DOI":"10.1016\/j.biopha.2019.109411","article-title":"LncRNA GAS5 exacerbates renal tubular epithelial fibrosis by acting as a competing endogenous RNA of miR-96-5p","volume":"121","author":"Wang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.molcel.2014.04.025","article-title":"LincRNA-p21 Activates p21 In cis to Promote Polycomb Target Gene Expression and to Enforce the G1\/S Checkpoint","volume":"54","author":"Dimitrova","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s10565-024-09874-5","article-title":"LncRNA KIFAP3-5:1 inhibits epithelial-mesenchymal transition of renal tubular cell through PRRX1 in diabetic nephropathy","volume":"40","author":"Du","year":"2024","journal-title":"Cell Biol. Toxicol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s12943-020-01286-3","article-title":"Circular RNA: Metabolism, functions and interactions with proteins","volume":"19","author":"Zhou","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1002\/jcp.26959","article-title":"Circular RNA circRNA_15698 aggravates the extracellular matrix of diabetic nephropathy mesangial cells via miR-185\/TGF-\u03b21","volume":"234","author":"Hu","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4520","DOI":"10.1002\/jcp.29329","article-title":"Circ_0080425 inhibits cell proliferation and fibrosis in diabetic nephropathy via sponging miR-24-3p and targeting fibroblast growth factor 11","volume":"235","author":"Liu","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_111","first-page":"3785","article-title":"A novel identified circular RNA, circ_0000491, aggravates the extracellular matrix of diabetic nephropathy glomerular mesangial cells through suppressing miR-101b by targeting TGF\u03b2RI","volume":"22","author":"Mou","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"144971","DOI":"10.1016\/j.gene.2020.144971","article-title":"Circ_0123996 promotes cell proliferation and fibrosis in mouse mesangial cells through sponging miR-149-5p and inducing Bach1 expression","volume":"761","author":"Wang","year":"2020","journal-title":"Gene"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"145076","DOI":"10.1016\/j.gene.2020.145076","article-title":"Circ_0037128\/miR-17-3p\/AKT3 axis promotes the development of diabetic nephropathy","volume":"765","author":"Wang","year":"2021","journal-title":"Gene"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ncrna.2025.05.003","article-title":"Circ_0054633 silencing suppresses hyperglycemia-induced extracellular matrix accumulation in renal mesangial cells by regulating MiR-136-5p\/SMAD3 signaling","volume":"13","author":"Jiang","year":"2025","journal-title":"Non-Coding RNA Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"8779","DOI":"10.1111\/jcmm.15513","article-title":"Circ-AKT3 inhibits the accumulation of extracellular matrix of mesangial cells in diabetic nephropathy via modulating miR-296-3p\/E-cadherin signals","volume":"24","author":"Tang","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"10646","DOI":"10.1002\/jcp.27744","article-title":"CircRNA ZNF609 functions as a competitive endogenous RNA to regulate FOXP4 expression by sponging miR-138-5p in renal carcinoma","volume":"234","author":"Xiong","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"145114","DOI":"10.1016\/j.gene.2020.145114","article-title":"Circ_LARP4 regulates high glucose-induced cell proliferation, apoptosis, and fibrosis in mouse mesangial cells","volume":"765","author":"Wang","year":"2021","journal-title":"Gene"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1038\/s41419-020-03169-3","article-title":"Exosomal circ_DLGAP4 promotes diabetic kidney disease progression by sponging miR-143 and targeting ERBB3\/NF-\u03baB\/MMP-2 axis","volume":"11","author":"Bai","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"145065","DOI":"10.1016\/j.gene.2020.145065","article-title":"Circular RNA HIPK3 exacerbates diabetic nephropathy and promotes proliferation by sponging miR-185","volume":"765","author":"Liu","year":"2021","journal-title":"Gene"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"118269","DOI":"10.1016\/j.lfs.2020.118269","article-title":"Circ_WBSCR17 aggravates inflammatory responses and fibrosis by targeting miR-185-5p\/SOX6 regulatory axis in high glucose-induced human kidney tubular cells","volume":"259","author":"Li","year":"2020","journal-title":"Life Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.2147\/DMSO.S265543","article-title":"Interference of Hsa_circ_0003928 Alleviates High Glucose-Induced Cell Apoptosis and Inflammation in HK-2 Cells via miR-151-3p\/Anxa2","volume":"13","author":"An","year":"2020","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1248\/bpb.b19-00901","article-title":"circACTR2: A Novel Mechanism Regulating High Glucose-Induced Fibrosis in Renal Tubular Cells via Pyroptosis","volume":"43","author":"Wen","year":"2020","journal-title":"Biol. Pharm. Bull."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1111\/jcmm.16129","article-title":"Circular RNA circEIF4G2 aggravates renal fibrosis in diabetic nephropathy by sponging miR-218","volume":"26","author":"Xu","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"729","DOI":"10.2147\/DMSO.S289624","article-title":"CircHIPK3 Alleviates High Glucose Toxicity to Human Renal Tubular Epithelial HK-2 Cells Through Regulation of miR-326\/miR-487a-3p\/SIRT1","volume":"14","author":"Zhuang","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"144661","DOI":"10.1016\/j.gene.2020.144661","article-title":"Circ_0000285 promotes podocyte injury through sponging miR-654-3p and activating MAPK6 in diabetic nephropathy","volume":"747","author":"Yao","year":"2020","journal-title":"Gene"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"603","DOI":"10.2337\/db20-0203","article-title":"circRNA_010383 Acts as a Sponge for miR-135a, and Its Downregulated Expression Contributes to Renal Fibrosis in Diabetic Nephropathy","volume":"70","author":"Peng","year":"2021","journal-title":"Diabetes"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/ki.2011.345","article-title":"Altered expression of microRNA miR-146a correlates with the development of chronic renal inflammation","volume":"81","author":"Ichii","year":"2012","journal-title":"Kidney Int."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1055\/s-0035-1565095","article-title":"Serum miR-21 may be a Potential Diagnostic Biomarker for Diabetic Nephropathy","volume":"124","author":"Wang","year":"2015","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.ymthe.2016.08.001","article-title":"Therapeutic miR-21 Silencing Ameliorates Diabetic Kidney Disease in Mice","volume":"25","author":"Kaucsar","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.jdiacomp.2015.12.011","article-title":"Downregulation of miR-30c promotes renal fibrosis by target CTGF in diabetic nephropathy","volume":"30","author":"Wang","year":"2016","journal-title":"J. Diabetes Its Complicat."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/acel.12563","article-title":"MiR-30c protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition in db\/db mice","volume":"16","author":"Zhao","year":"2017","journal-title":"Aging Cell"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/j.addr.2010.07.005","article-title":"Application of siRNA in targeting protein expression in kidney disease","volume":"62","author":"Stokman","year":"2010","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.apsb.2020.10.001","article-title":"Long non-coding RNAs: From disease code to drug role","volume":"11","author":"Chen","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cca.2017.08.038","article-title":"lncRNA PVT1 in cancer: A review and meta-analysis","volume":"474","author":"Lu","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.2147\/OTT.S190239","article-title":"LncRNA PVT1 promotes proliferation, invasion and epithelial\u2013mesenchymal transition of renal cell carcinoma cells through downregulation of miR-16-5p","volume":"12","author":"Ren","year":"2019","journal-title":"OncoTargets Ther."},{"key":"ref_136","first-page":"7855","article-title":"Knockdown of long non-coding RNA PVT1 induces apoptosis and cell cycle arrest in clear cell renal cell carcinoma through the epidermal growth factor receptor pathway","volume":"15","author":"Li","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/jcp.22783","article-title":"PAI-1 in tissue fibrosis","volume":"227","author":"Ghosh","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3892\/ijmm.2013.1234","article-title":"Plasminogen activator inhibitor-1 in kidney pathology","volume":"31","author":"Jankun","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Shi, S., Song, L., Yu, H., Feng, S., He, J., Liu, Y., and He, Y. (2020). Knockdown of LncRNA-H19 Ameliorates Kidney Fibrosis in Diabetic Mice by Suppressing miR-29a-Mediated EndMT. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.586895"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"51473","DOI":"10.18632\/oncotarget.10444","article-title":"Long non-coding RNA-H19 antagonism protects against renal fibrosis","volume":"7","author":"Xie","year":"2016","journal-title":"Oncotarget"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Shen, F., and Zhuang, S. (2022). Histone Acetylation and Modifiers in Renal Fibrosis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.760308"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"102674","DOI":"10.1016\/j.redox.2023.102674","article-title":"ROS promote hyper-methylation of NDRG2 promoters in a DNMTS-dependent manner: Contributes to the progression of renal fibrosis","volume":"62","author":"Zhao","year":"2023","journal-title":"Redox Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"6424","DOI":"10.1038\/srep06424","article-title":"siRNAs targeted to Smad4 prevent renal fibrosis in vivo","volume":"4","author":"Morishita","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3066","DOI":"10.1681\/ASN.2021040431","article-title":"CHOP-ASO Ameliorates Glomerular and Tubular Damage on Top of ACE Inhibition in Diabetic Kidney Disease","volume":"32","author":"Shahzad","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1089\/nat.2015.0598","article-title":"Comparative Renal Toxicopathology of Antisense Oligonucleotides","volume":"26","author":"Engelhardt","year":"2016","journal-title":"Nucleic Acid. Ther."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"102387","DOI":"10.1016\/j.omtn.2024.102387","article-title":"In vivo efficacy and safety of systemically administered serinol nucleic acid-modified antisense oligonucleotides in mouse kidney","volume":"36","author":"Tsuboi","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2469746","DOI":"10.1080\/0886022X.2025.2469746","article-title":"Lactate metabolism and lactylation in kidney diseases: Insights into mechanisms and therapeutic opportunities","volume":"47","author":"Cheng","year":"2025","journal-title":"Ren. Fail."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"103246","DOI":"10.1016\/j.redox.2024.103246","article-title":"Lactate drives epithelial-mesenchymal transition in diabetic kidney disease via the H3K14la\/KLF5 pathway","volume":"75","author":"Zhang","year":"2024","journal-title":"Redox Biol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"114498","DOI":"10.1016\/j.yexcr.2025.114498","article-title":"TGF-\u03b2-induced acetylation of KLF5 drives TNFAIP2 transcription and EMT in nasopharyngeal carcinoma: Unveiling a novel regulatory mechanism","volume":"447","author":"Qian","year":"2025","journal-title":"Exp. Cell Res."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Cai, R., Lv, R., Shi, X., Yang, G., and Jin, J. (2023). CRISPR\/dCas9 Tools: Epigenetic Mechanism and Application in Gene Transcriptional Regulation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914865"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4801\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T16:19:10Z","timestamp":1779812350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":150,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114801"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114801","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]}}}