{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:17:39Z","timestamp":1793121459330,"version":"4.5.0"},"reference-count":91,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The ubiquitin\u2013proteasome system (UPS) and autophagy maintain protein homeostasis, which is critical to cellular function and survival. The dysregulation of these pathways has been recognized as a hallmark of acute kidney injury and chronic kidney disease. This review elucidates the role of the UPS and autophagy in kidney disease, namely through inflammation, oxidative stress, fibrosis and apoptosis. The pathways of NF-\u03baB, TGF-\u03b2 and mitochondrial failure result in glomerular injury and tubulointerstitial fibrosis due to impaired proteostasis in podocytes and tubular epithelial cells. Recent studies have revealed a connection between the autophagic process and the UPS, wherein compensatory mechanisms aim to spike down proteotoxic stress but eventually seem inadequate in cases of chronic derangement. Low-dose pharmacological inhibitors, autophagy modulators, and new gene and nanotechnology-based treatments may all help to restore the protein balance and reduce kidney injury. A more thorough understanding of these pathways is needed to develop kidney-protective and disease-modifying therapeutic interventions.<\/jats:p>","DOI":"10.3390\/biom15030349","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T04:28:18Z","timestamp":1740716898000},"page":"349","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Renal Implications of Dysregulated Protein Homeostasis: Insights into Ubiquitin\u2013Proteasome and Autophagy Systems"],"prefix":"10.3390","volume":"15","author":[{"given":"Charlotte","family":"Delrue","sequence":"first","affiliation":[{"name":"Department of Nephrology, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9183-4390","authenticated-orcid":false,"given":"Marijn M.","family":"Speeckaert","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Ghent University Hospital, 9000 Ghent, Belgium"},{"name":"Research Foundation-Flanders (FWO), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chen, R.-H., Chen, Y.-H., and Huang, T.-Y. (2019). Ubiquitin-Mediated Regulation of Autophagy. J. Biomed. Sci., 26.","DOI":"10.1186\/s12929-019-0569-y"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, Y., Li, S., and Wu, H. (2022). Ubiquitination-Proteasome System (UPS) and Autophagy Two Main Protein Degradation Machineries in Response to Cell Stress. Cells, 11.","DOI":"10.3390\/cells11050851"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s10157-012-0643-1","article-title":"The Role of the Ubiquitin\u2013Proteasome System in Kidney Diseases","volume":"16","author":"Fukasawa","year":"2012","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_4","first-page":"222","article-title":"Proteasome Impairment Can Lead to CKD","volume":"17","author":"Carney","year":"2021","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1080\/15548627.2016.1159376","article-title":"Time-Dependent Dysregulation of Autophagy: Implications in Aging and Mitochondrial Homeostasis in the Kidney Proximal Tubule","volume":"12","author":"Yamamoto","year":"2016","journal-title":"Autophagy"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Vall\u00e9s, P.G., Gil Lorenzo, A.F., Garcia, R.D., Cacciamani, V., Benardon, M.E., and Costantino, V.V. (2023). Toll-like Receptor 4 in Acute Kidney Injury. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021415"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Cheng, C., Yuan, Y., Yuan, F., and Li, X. (2024). Acute Kidney Injury: Exploring Endoplasmic Reticulum Stress-Mediated Cell Death. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1308733"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lindholm, D., Korhonen, L., Eriksson, O., and K\u00f5ks, S. (2017). Recent Insights into the Role of Unfolded Protein Response in ER Stress in Health and Disease. Front. Cell Dev. Biol., 5.","DOI":"10.3389\/fcell.2017.00048"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6129","DOI":"10.1007\/s00253-020-10614-y","article-title":"Crosstalk between ER Stress, NLRP3 Inflammasome, and Inflammation","volume":"104","author":"Li","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ho, H.-J., and Shirakawa, H. (2022). Oxidative Stress and Mitochondrial Dysfunction in Chronic Kidney Disease. Cells, 12.","DOI":"10.3390\/cells12010088"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Alsayyah, C., Ozturk, O., Cavellini, L., Belgareh-Touz\u00e9, N., and Cohen, M.M. (2020). The Regulation of Mitochondrial Homeostasis by the Ubiquitin Proteasome System. Biochim. Biophys. Acta (BBA)-Bioenerg., 1861.","DOI":"10.1016\/j.bbabio.2020.148302"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lv, W., Booz, G.W., Fan, F., Wang, Y., and Roman, R.J. (2018). Oxidative Stress and Renal Fibrosis: Recent Insights for the Development of Novel Therapeutic Strategies. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00105"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Aranda-Rivera, A.K., Cruz-Gregorio, A., Pedraza-Chaverri, J., and Scholze, A. (2022). Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls. Antioxidants, 11.","DOI":"10.3390\/antiox11020246"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Isaka, Y. (2018). Targeting TGF-\u03b2 Signaling in Kidney Fibrosis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092532"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"607","DOI":"10.3390\/kidneydial2040055","article-title":"Cell\u2013Matrix Interactions in Renal Fibrosis","volume":"2","author":"Kim","year":"2022","journal-title":"Kidney Dial."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4161\/oxim.3.2.11148","article-title":"Advanced Glycation End Products, Oxidative Stress and Diabetic Nephropathy","volume":"3","author":"Yamagishi","year":"2010","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/978-981-13-8871-2_29","article-title":"Oxidative Stress and Renal Fibrosis: Mechanisms and Therapies","volume":"Volume 1165","author":"Liu","year":"2019","journal-title":"Renal Fibrosis: Mechanisms and Therapies"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s11926-018-0710-z","article-title":"Matrix Stiffness: The Conductor of Organ Fibrosis","volume":"20","author":"Santos","year":"2018","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1507\/endocrj.EJ20-0739","article-title":"Circular RNA Circ_0000712 Regulates High Glucose-Induced Apoptosis, Inflammation, Oxidative Stress, and Fibrosis in (DN) by Targeting the miR-879-5p\/SOX6 Axis","volume":"68","author":"Zhao","year":"2021","journal-title":"Endocr. J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Fois, A.G., Sotgiu, E., Scano, V., Negri, S., Mellino, S., Zinellu, E., Pirina, P., Pintus, G., Carru, C., and Mangoni, A.A. (2020). Effects of Pirfenidone and Nintedanib on Markers of Systemic Oxidative Stress and Inflammation in Patients with Idiopathic Pulmonary Fibrosis: A Preliminary Report. Antioxidants, 9.","DOI":"10.3390\/antiox9111064"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wei, J., Deng, H., Zheng, L., Yang, H., and Lv, X. (2022). The Role of Nrf2 in Pulmonary Fibrosis: Molecular Mechanisms and Treatment Approaches. Antioxidants, 11.","DOI":"10.3390\/antiox11091685"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41419-024-06449-4","article-title":"DDRGK1-Mediated ER-Phagy Attenuates Acute Kidney Injury through ER-Stress and Apoptosis","volume":"15","author":"Jin","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Huang, X., Liu, R., Zhan, C., Wu, H., Fan, J., Li, Z., and Yang, X. (2024). Aristolochic Acid Induces Acute Kidney Injury through Ferroptosis. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1330376"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s12964-023-01422-8","article-title":"Role of Ferroptosis in Chronic Kidney Disease","volume":"22","author":"Li","year":"2024","journal-title":"Cell Commun. Signal"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s12017-023-08755-0","article-title":"The Role of Ubiquitin\u2013Proteasome System and Mitophagy in the Pathogenesis of Parkinson\u2019s Disease","volume":"25","author":"Liang","year":"2023","journal-title":"Neuromol Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Morgan, J.J., and Crawford, L.J. (2021). The Ubiquitin Proteasome System in Genome Stability and Cancer. Cancers, 13.","DOI":"10.3390\/cancers13092235"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1126\/science.aax3769","article-title":"Cellular Quality Control by the Ubiquitin-Proteasome System and Autophagy","volume":"366","author":"Pohl","year":"2019","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1007\/s13238-017-0486-3","article-title":"The Role of Ubiquitination and Deubiquitination in the Regulation of Cell Junctions","volume":"9","author":"Cai","year":"2018","journal-title":"Protein Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00432-017-2557-5","article-title":"Targeting LC3 and Beclin-1 Autophagy Genes Suppresses Proliferation, Survival, Migration and Invasion by Inhibition of Cyclin-D1 and uPAR\/Integrin \u03921\/Src Signaling in Triple Negative Breast Cancer Cells","volume":"144","author":"Hamurcu","year":"2018","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1080\/15548627.2019.1580512","article-title":"Podocytes and Autophagy: A Potential Therapeutic Target in Lupus Nephritis","volume":"15","author":"Zhou","year":"2019","journal-title":"Autophagy"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.jdiacomp.2015.07.021","article-title":"The Renoprotective Role of Autophagy Activation in Proximal Tubular Epithelial Cells in Diabetic Nephropathy","volume":"29","author":"Xu","year":"2015","journal-title":"J. Diabetes Its Complicat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/ki.2012.390","article-title":"The Intersecting Roles of Endoplasmic Reticulum Stress, Ubiquitin\u2013Proteasome System, and Autophagy in the Pathogenesis of Proteinuric Kidney Disease","volume":"84","author":"Cybulsky","year":"2013","journal-title":"Kidney Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.2337\/db16-0397","article-title":"Autophagy Inhibits the Accumulation of Advanced Glycation End Products by Promoting Lysosomal Biogenesis and Function in the Kidney Proximal Tubules","volume":"66","author":"Takahashi","year":"2017","journal-title":"Diabetes"},{"key":"ref_34","first-page":"1","article-title":"Podocyte Autophagy: A Potential Therapeutic Target to Prevent the Progression of Diabetic Nephropathy","volume":"2017","author":"Liu","year":"2017","journal-title":"J. Diabetes Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s00109-018-1656-3","article-title":"Deregulation of Autophagy under Hyperglycemic Conditions Is Dependent on Increased Lysine 63 Ubiquitination: A Candidate Mechanism in the Progression of Diabetic Nephropathy","volume":"96","author":"Pontrelli","year":"2018","journal-title":"J. Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/s41581-019-0148-1","article-title":"The Ubiquitin\u2013Proteasome System in Kidney Physiology and Disease","volume":"15","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gong, Y., Zhu, W., Li, Y., Lu, T., Tan, J., He, C., Yang, L., Zhu, Y., and Gong, L. (2024). Dynamic Regulation of Proximal Tubular Autophagy from Injury to Repair after Ischemic Kidney Damage. Cell Mol. Biol. Lett., 29.","DOI":"10.1186\/s11658-024-00663-w"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s11255-016-1247-6","article-title":"Proteasome or Immunoproteasome Inhibitors Cause Apoptosis in Human Renal Tubular Epithelial Cells under Normoxic and Hypoxic Conditions","volume":"48","author":"Eleftheriadis","year":"2016","journal-title":"Int. Urol. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rauert-Wunderlich, H., Siegmund, D., Maier, E., Giner, T., Bargou, R.C., Wajant, H., and St\u00fchmer, T. (2013). The IKK Inhibitor Bay 11-7082 Induces Cell Death Independent from Inhibition of Activation of NF\u03baB Transcription Factors. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059292"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1093\/ckj\/sfv059","article-title":"Thrombotic Microangiopathy Associated with Proteasome Inhibitors","volume":"8","author":"Lodhi","year":"2015","journal-title":"Clin. Kidney J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1159\/000475890","article-title":"Targeting the KEAP1-NRF2 System to Prevent Kidney Disease Progression","volume":"45","author":"Nezu","year":"2017","journal-title":"Am. J. Nephrol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Li, S.-S., Sun, Q., Hua, M.-R., Suo, P., Chen, J.-R., Yu, X.-Y., and Zhao, Y.-Y. (2021). Targeting the Wnt\/\u03b2-Catenin Signaling Pathway as a Potential Therapeutic Strategy in Renal Tubulointerstitial Fibrosis. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.719880"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Delrue, C., Eisenga, M.F., Delanghe, J.R., and Speeckaert, M.M. (2024). Personalized Antifibrotic Therapy in CKD Progression. J. Pers. Med., 14.","DOI":"10.3390\/jpm14121141"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1007\/s13300-024-01641-3","article-title":"Targeting Autophagy: A Promising Therapeutic Strategy for Diabetes Mellitus and Diabetic Nephropathy","volume":"15","author":"Li","year":"2024","journal-title":"Diabetes Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1007\/s12079-023-00781-8","article-title":"Metformin Combined with Rapamycin Ameliorates Podocyte Injury in Idiopathic Membranous Nephropathy through the AMPK\/mTOR Signaling Pathway","volume":"17","author":"Ma","year":"2023","journal-title":"J. Cell Commun. Signal."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kench, U., Sologova, S., Smolyarchuk, E., Prassolov, V., and Spirin, P. (2024). Pharmaceutical Agents for Targeting Autophagy and Their Applications in Clinics. Pharmaceuticals, 17.","DOI":"10.3390\/ph17101355"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/s41419-021-04184-8","article-title":"AMPK Agonist Alleviate Renal Tubulointerstitial Fibrosis via Activating Mitophagy in High Fat and Streptozotocin Induced Diabetic Mice","volume":"12","author":"Han","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Dai, R., Zhang, L., Jin, H., Wang, D., Cheng, M., Sang, T., Peng, C., Li, Y., and Wang, Y. (2022). Autophagy in Renal Fibrosis: Protection or Promotion?. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.963920"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhang, Y.-Y., Zhou, X.-T., Huang, G.-Z., Liao, W.-J., Chen, X., and Ma, Y.-R. (2024). The Pro-Fibrotic Role of Autophagy in Renal Intrinsic Cells: Mechanisms and Therapeutic Potential in Chronic Kidney Disease. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1499457"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Gu\u00e9dat, P., and Colland, F. (2007). Patented Small Molecule Inhibitors in the Ubiquitin Proteasome System. BMC Biochem., 8.","DOI":"10.1186\/1471-2091-8-S1-S14"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.trim.2012.01.002","article-title":"Proteasome Inhibition by Bortezomib: Effect on HLA-Antibody Levels and Specificity in Sensitized Patients Awaiting Renal Allograft Transplantation","volume":"26","author":"Guthoff","year":"2012","journal-title":"Transplant. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1182\/blood.2019000834","article-title":"A Prospective Observational Study of 915 Patients with Systemic AL Amyloidosis Treated with Upfront Bortezomib","volume":"134","author":"Manwani","year":"2019","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.ctrv.2005.10.001","article-title":"Bortezomib, a Novel Proteasome Inhibitor, in the Treatment of Hematologic Malignancies","volume":"31","author":"Jackson","year":"2005","journal-title":"Cancer Treat. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.2174\/1381612811319220012","article-title":"From Bortezomib to Other Inhibitors of the Proteasome and Beyond","volume":"19","author":"Buac","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Muchamuel, T., Fan, R.A., Anderl, J.L., Bomba, D.J., Johnson, H.W.B., Lowe, E., Tuch, B.B., McMinn, D.L., Millare, B., and Kirk, C.J. (2023). Zetomipzomib (KZR-616) Attenuates Lupus in Mice via Modulation of Innate and Adaptive Immune Responses. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1043680"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1016\/j.bbamcr.2012.05.005","article-title":"Ubiquitin-Based Anticancer Therapy: Carpet Bombing with Proteasome Inhibitors vs Surgical Strikes with E1, E2, E3, or DUB Inhibitors","volume":"1823","author":"Mattern","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Zeng, W., Qi, W., Mu, J., Wei, Y., Yang, L.-L., Zhang, Q., Wu, Q., Tang, J.-Y., and Feng, B. (2019). MG132 Protects against Renal Dysfunction by Regulating Akt-Mediated Inflammation in Diabetic Nephropathy. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-38425-2"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1093\/ndt\/gfy407","article-title":"SGLT-2 Inhibitors and GLP-1 Receptor Agonists for Nephroprotection and Cardioprotection in Patients with Diabetes Mellitus and Chronic Kidney Disease. A Consensus Statement by the EURECA-m and the DIABESITY Working Groups of the ERA-EDTA","volume":"34","author":"Sarafidis","year":"2019","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Rakotoarison, A., Kepinska, M., Konieczny, A., W\u0142adyczak, K., Janczak, D., Ha\u0142o\u0144, A., Donizy, P., and Banasik, M. (2024). Endothelin Inhibitors in Chronic Kidney Disease: New Treatment Prospects. J. Clin. Med., 13.","DOI":"10.3390\/jcm13206056"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"TPS678","DOI":"10.1200\/JCO.2019.37.7_suppl.TPS678","article-title":"Phase II Trial of Ixazomib Combined with Gemcitabine and Doxorubicin in Patients with SMARCB1-Deficient Kidney Malignancies","volume":"37","author":"Msaouel","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"F777","DOI":"10.1152\/ajprenal.00590.2007","article-title":"Autophagy Is Associated with Apoptosis in Cisplatin Injury to Renal Tubular Epithelial Cells","volume":"294","author":"Yang","year":"2008","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Sheng, H., Zhang, D., Zhang, J., Zhang, Y., Lu, Z., Mao, W., Liu, X., and Zhang, L. (2022). Kaempferol Attenuated Diabetic Nephropathy by Reducing Apoptosis and Promoting Autophagy through AMPK\/mTOR Pathways. Front. Med., 9.","DOI":"10.3389\/fmed.2022.986825"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Yuan, T., Yan, F., Ying, M., Cao, J., He, Q., Zhu, H., and Yang, B. (2018). Inhibition of Ubiquitin-Specific Proteases as a Novel Anticancer Therapeutic Strategy. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01080"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/j.biocel.2012.07.011","article-title":"Proteasome Deubiquitinases as Novel Targets for Cancer Therapy","volume":"44","author":"Linder","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1182\/blood.V114.22.610.610","article-title":"Deubiquitylating Enzyme USP-7, a Novel Therapeutic Target in Multiple Myeloma","volume":"114","author":"Chauhan","year":"2009","journal-title":"Blood"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"gfac074.023","DOI":"10.1093\/ndt\/gfac074.023","article-title":"MO578: UBE-1099, A Novel Non-Covalent Keap1-NRF2 Inhibitor, Protects Against Renal Ischemia-Reperfusion Injury","volume":"37","author":"Ogi","year":"2022","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1021\/acsmedchemlett.3c00067","article-title":"Methyl and Fluorine Effects in Novel Orally Bioavailable Keap1\u2013Nrf2 PPI Inhibitor","volume":"14","author":"Otake","year":"2023","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41401-019-0297-6","article-title":"A Novel Compound AB38b Attenuates Oxidative Stress and ECM Protein Accumulation in Kidneys of Diabetic Mice through Modulation of Keap1\/Nrf2 Signaling","volume":"41","author":"Du","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"13774","DOI":"10.1074\/jbc.M117.791483","article-title":"Forkhead Box O3 (FoxO3) Regulates Kidney Tubular Autophagy Following Urinary Tract Obstruction","volume":"292","author":"Li","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s10924-024-03451-x","article-title":"Fabrication of Co-Delivery of Bortezomib and Vincristine Loaded Chitosan Cross-Linked Polymeric Nanoparticles: Evaluation of Anticancer Activity and Apoptosis Induction in Lung Cancer Cells","volume":"33","author":"Sun","year":"2024","journal-title":"J. Polym. Environ."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1700585","DOI":"10.1002\/advs.201700585","article-title":"Titania-Coated Gold Nano-Bipyramids for Blocking Autophagy Flux and Sensitizing Cancer Cells to Proteasome Inhibitor-Induced Death","volume":"5","author":"Wan","year":"2018","journal-title":"Adv. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Lu, M.-C., Zhao, J., Liu, Y.-T., Liu, T., Tao, M.-M., You, Q.-D., and Jiang, Z.-Y. (2019). CPUY192018, a Potent Inhibitor of the Keap1-Nrf2 Protein-Protein Interaction, Alleviates Renal Inflammation in Mice by Restricting Oxidative Stress and NF-\u03baB Activation. Redox Biol., 26.","DOI":"10.1016\/j.redox.2019.101266"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1080\/15548627.2015.1049799","article-title":"Endothelial Cell and Podocyte Autophagy Synergistically Protect from Diabetes-Induced Glomerulosclerosis","volume":"11","author":"Lenoir","year":"2015","journal-title":"Autophagy"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Zeng, Y., Yang, X., Wang, J., Fan, J., Kong, Q., and Yu, X. (2012). Aristolochic Acid I Induced Autophagy Extenuates Cell Apoptosis via ERK 1\/2 Pathway in Renal Tubular Epithelial Cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030312"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Ruby, M., Gifford, C.C., Pandey, R., Raj, V.S., Sabbisetti, V.S., and Ajay, A.K. (2023). Autophagy as a Therapeutic Target for Chronic Kidney Disease and the Roles of TGF-\u03921 in Autophagy and Kidney Fibrosis. Cells, 12.","DOI":"10.3390\/cells12030412"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"20499","DOI":"10.1074\/jbc.M115.666354","article-title":"Autophagy-Lysosome Pathway in Renal Tubular Epithelial Cells Is Disrupted by Advanced Glycation End Products in Diabetic Nephropathy","volume":"290","author":"Liu","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_77","first-page":"4946","article-title":"The Inhibition of SGK1 Suppresses Epithelial-Mesenchymal Transition and Promotes Renal Tubular Epithelial Cell Autophagy in Diabetic Nephropathy","volume":"11","author":"Zhuang","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Jones, T.M., Carew, J.S., and Nawrocki, S.T. (2020). Therapeutic Targeting of Autophagy for Renal Cell Carcinoma Therapy. Cancers, 12.","DOI":"10.3390\/cancers12051185"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.2147\/DMSO.S299375","article-title":"Emodin Ameliorates Renal Damage and Podocyte Injury in a Rat Model of Diabetic Nephropathy via Regulating AMPK\/mTOR-Mediated Autophagy Signaling Pathway","volume":"14","author":"Liu","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ejphar.2018.02.009","article-title":"Mangiferin Prevents Diabetic Nephropathy Progression and Protects Podocyte Function via Autophagy in Diabetic Rat Glomeruli","volume":"824","author":"Wang","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"109744","DOI":"10.1016\/j.cellsig.2020.109744","article-title":"HGF Protected Against Diabetic Nephropathy via Autophagy-Lysosome Pathway in Podocyte by Modulating PI3K\/Akt-GSK3\u03b2-TFEB Axis","volume":"75","author":"Hou","year":"2020","journal-title":"Cell Signal."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Vainshtein, A., and Grumati, P. (2020). Selective Autophagy by Close Encounters of the Ubiquitin Kind. Cells, 9.","DOI":"10.3390\/cells9112349"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Hillmann, P., and Fabbro, D. (2019). PI3K\/mTOR Pathway Inhibition: Opportunities in Oncology and Rare Genetic Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225792"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"22426","DOI":"10.1074\/jbc.M110.149252","article-title":"Dynamics of the Degradation of Ubiquitinated Proteins by Proteasomes and Autophagy","volume":"286","author":"Myeku","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s11010-024-05042-9","article-title":"Mitophagy in Relation to Chronic Inflammation\/ROS in Aging","volume":"480","author":"Kong","year":"2024","journal-title":"Mol. Cell Biochem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5740","DOI":"10.1111\/jcmm.15236","article-title":"Mindin Deficiency Alleviates Renal Fibrosis through Inhibiting NF-\u03baB and TGF-\u03b2\/Smad Pathways","volume":"24","author":"Yang","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1038\/sj.ki.5001543","article-title":"Rapamycin and Chronic Kidney Disease: Beyond the Inhibition of Inflammation","volume":"69","author":"Liu","year":"2006","journal-title":"Kidney Int."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.kint.2020.08.020","article-title":"Preoperative Carfilzomib and Lulizumab Based Desensitization Prolongs Graft Survival in a Sensitized Non-Human Primate Model","volume":"99","author":"Schroder","year":"2021","journal-title":"Kidney Int."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.ekir.2020.03.022","article-title":"Use of Bortezomib in the Treatment of C3 Glomerulonephritis Refractory to Eculizumab and Rituximab","volume":"5","author":"Hui","year":"2020","journal-title":"Kidney Int. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Zheng, H., Zhang, Y., He, J., Yang, Z., Zhang, R., Li, L., Luo, Z., Ye, Y., and Sun, Q. (2021). Hydroxychloroquine Inhibits Macrophage Activation and Attenuates Renal Fibrosis After Ischemia-Reperfusion Injury. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.645100"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Delrue, C., and Speeckaert, M.M. (2024). Decoding Kidney Pathophysiology: Omics-Driven Approaches in Precision Medicine. J. Pers. Med., 14.","DOI":"10.3390\/jpm14121157"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/3\/349\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:44:14Z","timestamp":1760028254000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/3\/349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,28]]},"references-count":91,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["biom15030349"],"URL":"https:\/\/doi.org\/10.3390\/biom15030349","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,28]]}}}