{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:20:49Z","timestamp":1793413249342,"version":"4.5.0"},"reference-count":117,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570975"],"award-info":[{"award-number":["82570975"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005046","name":"National Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"crossref","award":["QC2025H014"],"award-info":[{"award-number":["QC2025H014"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Doctoral Research Foundation of Mudanjiang Medical University","award":["2023-MYBSKY-012"],"award-info":[{"award-number":["2023-MYBSKY-012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Kidney fibrosis is the final common pathological pathway through which chronic kidney disease progresses to end-stage kidney disease, yet therapies designed specifically to interrupt the core fibrotic process in the kidney are still lacking. This unmet need reflects the biological heterogeneity of kidney fibrosis, the context-dependent interplay among inflammatory, metabolic and mechanical signals, and the limited translational value of many conventional preclinical models. The mechanistic landscape has also broadened considerably beyond canonical transforming growth factor-\u03b2 signaling, now encompassing immune\u2013stromal crosstalk, metabolic rewiring, mechanotransduction, epigenetic reprogramming, and extracellular vesicle-mediated communication. These developments have brought several druggable nodes into view and may support more selective and durable antifibrotic interventions. At the same time, translational platforms including artificial intelligence-assisted in silico screening, patient-derived kidney organoids, bioengineered tissue systems, and refined animal models are changing how targets are discovered and pharmacologically validated. In this review, we examine emerging mechanisms that govern kidney fibrogenesis, with emphasis on therapeutic tractability, and consider how experimental models can improve target prioritization and drug development. We also summarize repurposed drugs, pathway-targeted agents, receptor-directed strategies, and cell-based approaches under preclinical or clinical evaluation. We close by discussing key barriers to clinical translation, including disease heterogeneity, inadequate biomarkers, and the need to balance antifibrotic efficacy with renal safety. A pharmacology driven framework that links mechanism, model, and patient stratification could help accelerate precision antifibrotic therapy for kidney disease.<\/jats:p>","DOI":"10.1093\/ckj\/sfag275","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:46:52Z","timestamp":1786535212000},"source":"Crossref","is-referenced-by-count":1,"title":["Pharmacological targeting of kidney fibrosis: druggable mechanisms, translational models, and emerging antifibrotic therapies"],"prefix":"10.1093","volume":"19","author":[{"given":"Peijian","family":"Chen","sequence":"first","affiliation":[{"name":"College of Life Sciences, Mudanjiang Medical University , Mudanjiang, Heilongjiang ,","place":["PR China"]},{"name":"Heilongjiang Province Key Laboratory for Anti-fibrosis Biotherapy, Mudanjiang Medical University , Mudanjiang, Heilongjiang ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Mudanjiang Medical University , Mudanjiang, Heilongjiang ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minglu","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Graduate Studies, Mudanjiang Medical University , Mudanjiang, Heilongjiang ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhui","family":"Chu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Mudanjiang Medical University , Mudanjiang, Heilongjiang ,","place":["PR China"]},{"name":"Heilongjiang Province Key Laboratory for Anti-fibrosis Biotherapy, Mudanjiang Medical University , Mudanjiang, Heilongjiang ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingru","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Mudanjiang Medical University , Mudanjiang, Heilongjiang ,","place":["PR China"]},{"name":"Heilongjiang Province Key Laboratory for Anti-fibrosis Biotherapy, Mudanjiang Medical University , Mudanjiang, Heilongjiang ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"2026090409012127300_bib1","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1016\/j.stem.2022.06.005","article-title":"A scalable organoid model of human autosomal dominant polycystic kidney disease for disease mechanism and drug discovery","volume":"29","author":"Tran","year":"2022","journal-title":"Cell Stem Cell"},{"key":"2026090409012127300_bib2","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/s41392-023-01379-7","article-title":"Kidney fibrosis: from mechanisms to therapeutic medicines","volume":"8","author":"Huang","year":"2023","journal-title":"Sig Transduct Target Ther"},{"key":"2026090409012127300_bib3","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/s41392-022-01070-3","article-title":"Targeting fibrosis: mechanisms and clinical trials","volume":"7","author":"Zhao","year":"2022","journal-title":"Sig Transduct Target Ther"},{"key":"2026090409012127300_bib4","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.7150\/ijbs.101548","article-title":"Modulation of TGF-\u03b2 signaling new approaches toward kidney disease and fibrosis therapy","volume":"21","author":"Hong","year":"2025","journal-title":"Int J Biol Sci"},{"key":"2026090409012127300_bib5","doi-asserted-by":"publisher","first-page":"2795","DOI":"10.7150\/ijbs.71595","article-title":"Smad3 Signatures in renal inflammation and fibrosis","volume":"18","author":"Wu","year":"2022","journal-title":"Int J Biol Sci"},{"key":"2026090409012127300_bib6","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41419-022-05138-4","article-title":"GSDMD-dependent neutrophil extracellular traps promote macrophage-to-myofibroblast transition and renal fibrosis in obstructive nephropathy","volume":"13","author":"Wang","year":"2022","journal-title":"Cell Death Dis"},{"key":"2026090409012127300_bib7","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1681\/ASN.0000000000000328","article-title":"WWP2 regulates renal fibrosis and the metabolic reprogramming of profibrotic myofibroblasts","volume":"35","author":"Chen","year":"2024","journal-title":"J Am Soc Nephrol"},{"key":"2026090409012127300_bib8","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/s41573-025-01158-9","article-title":"Fibrosis: cross-organ biology and pathways to development of innovative drugs","volume":"24","author":"Rieder","year":"2025","journal-title":"Nat Rev Drug Discov"},{"key":"2026090409012127300_bib9","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1038\/s41467-025-67373-5","article-title":"Tracing the origin of myofibroblasts in kidney fibrosis","volume":"17","author":"He","year":"2025","journal-title":"Nat Commun"},{"key":"2026090409012127300_bib10","doi-asserted-by":"publisher","first-page":"22508","DOI":"10.1021\/acsnano.3c05998","article-title":"Precisely regulating M2 subtype macrophages for renal fibrosis resolution","volume":"17","author":"Luo","year":"2023","journal-title":"ACS Nano"},{"key":"2026090409012127300_bib11","doi-asserted-by":"publisher","first-page":"F907","DOI":"10.1152\/ajprenal.00059.2025","article-title":"Single-cell RNA sequencing and spatial transcriptomics reveal unique subpopulations of infiltrating macrophages and dendritic cells following AKI","volume":"328","author":"Melkonian","year":"2025","journal-title":"Am J Physiol Renal Physiol"},{"key":"2026090409012127300_bib12","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nat Immunol"},{"key":"2026090409012127300_bib13","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/s41586-019-1631-3","article-title":"Resolving the fibrotic niche of human liver cirrhosis at single cell level","volume":"575","author":"Ramachandran","year":"2019","journal-title":"Nature"},{"key":"2026090409012127300_bib14","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.bbrc.2022.06.008","article-title":"HIF-1\u03b1 mediates renal fibrosis by regulating metabolic remodeling of renal tubule epithelial cells","volume":"618","author":"Liu","year":"2022","journal-title":"Biochem Biophys Res Commun"},{"key":"2026090409012127300_bib15","doi-asserted-by":"publisher","first-page":"C999","DOI":"10.1152\/ajpcell.00201.2023","article-title":"Hypoxia and renal fibrosis","volume":"325","author":"Naas","year":"2023","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026090409012127300_bib16","doi-asserted-by":"publisher","first-page":"155913","DOI":"10.1016\/j.metabol.2024.155913","article-title":"Role of mitochondria in pathogenesis and therapy of renal fibrosis","volume":"155","author":"Zhao","year":"2024","journal-title":"Metabolism"},{"key":"2026090409012127300_bib17","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.ymthe.2024.12.053","article-title":"ATGL regulates renal fibrosis by reprogramming lipid metabolism during the transition from AKI to CKD","volume":"33","author":"Li","year":"2025","journal-title":"Mol Ther"},{"key":"2026090409012127300_bib18","doi-asserted-by":"publisher","first-page":"174503","DOI":"10.1016\/j.ejphar.2021.174503","article-title":"Pirfenidone is a renal protective drug: mechanisms, signalling pathways, and preclinical evidence","volume":"911","author":"Bai","year":"2021","journal-title":"Eur J Pharmacol"},{"key":"2026090409012127300_bib19","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.3390\/ph17091147","article-title":"Safety of nintedanib in a patient with chronic pulmonary fibrosis and kidney disease","volume":"17","author":"Maggisano","year":"2024","journal-title":"Pharmaceuticals"},{"key":"2026090409012127300_bib20","doi-asserted-by":"publisher","first-page":"e23529","DOI":"10.1002\/dvg.23529","article-title":"Epithelial-mesenchymal plasticity in kidney fibrosis","volume":"62","author":"Hadpech","year":"2024","journal-title":"Genesis"},{"key":"2026090409012127300_bib21","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/ki.2014.287","article-title":"Origin of myofibroblasts and cellular events triggering fibrosis","volume":"87","author":"Mack","year":"2015","journal-title":"Kidney Int"},{"key":"2026090409012127300_bib22","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1152\/physrev.00027.2022","article-title":"Obstructive nephropathy and molecular pathophysiology of renal interstitial fibrosis","volume":"103","author":"N\u00f8rregaard","year":"2023","journal-title":"Physiol Rev"},{"key":"2026090409012127300_bib23","doi-asserted-by":"publisher","first-page":"115708","DOI":"10.1016\/j.fct.2025.115708","article-title":"Aristolochic acid I promotes renal tubulointerstitial fibrosis by activating the mannan-binding lectin serine protease 1-complement system","volume":"205","author":"Wang","year":"2025","journal-title":"Food Chem Toxicol"},{"key":"2026090409012127300_bib24","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/nrneph.2011.16","article-title":"Pathophysiology of ischemic acute kidney injury","volume":"7","author":"Sharfuddin","year":"2011","journal-title":"Nat Rev Nephrol"},{"key":"2026090409012127300_bib25","doi-asserted-by":"publisher","first-page":"4210","DOI":"10.1172\/JCI45161","article-title":"Cellular pathophysiology of ischemic acute kidney injury","volume":"121","author":"Bonventre","year":"2011","journal-title":"J Clin Invest"},{"key":"2026090409012127300_bib26","doi-asserted-by":"publisher","first-page":"3346","DOI":"10.1038\/s41598-025-86496-9","article-title":"UHRF1 promotes epithelial-mesenchymal transition mediating renal fibrosis by activating the TGF-\u03b2\/SMAD signaling pathway","volume":"15","author":"Yang","year":"2025","journal-title":"Sci Rep"},{"key":"2026090409012127300_bib27","doi-asserted-by":"publisher","first-page":"F788","DOI":"10.1152\/ajprenal.00184.2024","article-title":"Transition from acute kidney injury to chronic kidney disease: mechanisms, models, and biomarkers","volume":"327","author":"Zhang","year":"2024","journal-title":"Am J Physiol Renal Physiol"},{"key":"2026090409012127300_bib28","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1093\/ndt\/gfad238","article-title":"Endothelial to mesenchymal transition in kidney fibrosis","volume":"39","author":"Jacobs","year":"2024","journal-title":"Nephrol Dial Transplant"},{"key":"2026090409012127300_bib29","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.kint.2022.05.012","article-title":"Molecular mechanisms and therapeutic targets for diabetic kidney disease","volume":"102","author":"Tuttle","year":"2022","journal-title":"Kidney Int"},{"key":"2026090409012127300_bib30","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrneph.2016.75","article-title":"Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis","volume":"12","author":"VD","year":"2016","journal-title":"Nat Rev Nephrol"},{"key":"2026090409012127300_bib31","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.3390\/biomedicines12051098","article-title":"Diabetes and renal complications: an overview on pathophysiology, biomarkers and therapeutic interventions","volume":"12","author":"Jha","year":"2024","journal-title":"Biomedicines"},{"key":"2026090409012127300_bib32","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.ejphar.2018.06.001","article-title":"AGE-RAGE axis blockade in diabetic nephropathy: current status and future directions","volume":"833","author":"Sanajou","year":"2018","journal-title":"Eur J Pharmacol"},{"key":"2026090409012127300_bib33","doi-asserted-by":"publisher","first-page":"5405","DOI":"10.7150\/ijbs.75876","article-title":"The role of IL-6 in fibrotic diseases: molecular and cellular mechanisms","volume":"18","author":"Li","year":"2022","journal-title":"Int J Biol Sci"},{"key":"2026090409012127300_bib34","doi-asserted-by":"publisher","first-page":"103466","DOI":"10.1016\/j.autrev.2023.103466","article-title":"From inflammation to renal fibrosis: a one-way road in autoimmunity?","volume":"23","author":"Roccatello","year":"2024","journal-title":"Autoimmun Rev"},{"key":"2026090409012127300_bib35","doi-asserted-by":"publisher","first-page":"14317","DOI":"10.3390\/ijms232214317","article-title":"Renal fibrosis in lupus nephritis","volume":"23","author":"Sciascia","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026090409012127300_bib36","doi-asserted-by":"publisher","first-page":"117","DOI":"10.3389\/fimmu.2016.00117","article-title":"The origin and activities of IgA1-containing immune complexes in IgA nephropathy","volume":"7","author":"Knoppova","year":"2016","journal-title":"Front Immunol"},{"key":"2026090409012127300_bib37","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1093\/ndt\/gfae292","article-title":"Infiltrative classical monocyte-derived and SPP1 lipid-associated macrophages mediate inflammation and fibrosis in ANCA-associated glomerulonephritis","volume":"40","author":"Vegting","year":"2025","journal-title":"Nephrol Dial Transplant"},{"key":"2026090409012127300_bib38","doi-asserted-by":"publisher","first-page":"20920","DOI":"10.1038\/s41598-021-00392-6","article-title":"Cumulative DNA damage by repeated low-dose cisplatin injection promotes the transition of acute to chronic kidney injury in mice","volume":"11","author":"Yamashita","year":"2021","journal-title":"Sci Rep"},{"key":"2026090409012127300_bib39","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1111\/j.1523-1755.2004.00720.x","article-title":"Nephrotoxicity of platinum complexes is related to basolateral organic cation transport","volume":"66","author":"Ludwig","year":"2004","journal-title":"Kidney Int"},{"key":"2026090409012127300_bib40","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1681\/ASN.V134866","article-title":"Gene expression levels and immunolocalization of organic ion transporters in the human kidney","volume":"13","author":"Motohashi","year":"2002","journal-title":"J Am Soc Nephrol"},{"key":"2026090409012127300_bib41","doi-asserted-by":"publisher","first-page":"103179","DOI":"10.1016\/j.redox.2024.103179","article-title":"Mitochondrial GPX4 acetylation is involved in cadmium-induced renal cell ferroptosis","volume":"73","author":"Guo","year":"2024","journal-title":"Redox Biol"},{"key":"2026090409012127300_bib42","doi-asserted-by":"publisher","first-page":"1718695","DOI":"10.3389\/fimmu.2025.1718695","article-title":"Effects of heavy metal exposure on kidney transplant recipients: mechanisms and clinical implications for graft failure risk","volume":"16","author":"Li","year":"2025","journal-title":"Front Immunol"},{"key":"2026090409012127300_bib43","doi-asserted-by":"publisher","first-page":"489","DOI":"10.3390\/cells13060489","article-title":"CD74 promotes cyst growth and renal fibrosis in autosomal dominant polycystic kidney disease","volume":"13","author":"Zhou","year":"2024","journal-title":"Cells"},{"key":"2026090409012127300_bib44","doi-asserted-by":"publisher","first-page":"100631","DOI":"10.1016\/j.xkme.2023.100631","article-title":"Alport syndrome: clinical spectrum and therapeutic advances","volume":"5","author":"Gregorio","year":"2023","journal-title":"Kidney Medicine"},{"key":"2026090409012127300_bib45","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/s41419-023-06209-w","article-title":"Kidney tubular epithelial cells control interstitial fibroblast fate by releasing TNFAIP8-encapsulated exosomes","volume":"14","author":"Liu","year":"2023","journal-title":"Cell Death Dis"},{"key":"2026090409012127300_bib46","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.1093\/ndt\/gfaa079","article-title":"Macrophage interactions with collecting duct epithelial cells are capable of driving tubulointerstitial inflammation and fibrosis in immunoglobulin A nephropathy","volume":"35","author":"Pawluczyk","year":"2020","journal-title":"Nephrol Dial Transplant"},{"key":"2026090409012127300_bib47","doi-asserted-by":"publisher","first-page":"2915","DOI":"10.1113\/JP286756","article-title":"Tumour necrosis factor-alpha at the intersection of renal epithelial and immune cell function","volume":"603","author":"Hubbi","year":"2025","journal-title":"J Physiol"},{"key":"2026090409012127300_bib48","doi-asserted-by":"publisher","first-page":"324","DOI":"10.7150\/thno.63735","article-title":"Tubular epithelial cell-to-macrophage communication forms a negative feedback loop via extracellular vesicle transfer to promote renal inflammation and apoptosis in diabetic nephropathy","volume":"12","author":"Jiang","year":"2022","journal-title":"Theranostics"},{"key":"2026090409012127300_bib49","doi-asserted-by":"publisher","first-page":"3007","DOI":"10.1038\/s41467-023-38771-4","article-title":"HDAC9-mediated epithelial cell cycle arrest in G2\/M contributes to kidney fibrosis in male mice","volume":"14","author":"Zhang","year":"2023","journal-title":"Nat Commun"},{"key":"2026090409012127300_bib50","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1038\/s41418-020-00631-9","article-title":"Histone deacetylase 3 aberration inhibits Klotho transcription and promotes renal fibrosis","volume":"28","author":"Chen","year":"2021","journal-title":"Cell Death Differ"},{"key":"2026090409012127300_bib51","doi-asserted-by":"publisher","first-page":"1497026","DOI":"10.3389\/fimmu.2024.1497026","article-title":"The role and therapeutic targeting of the CCL2\/CCR2 signaling axis in inflammatory and fibrotic diseases","volume":"15","author":"Guo","year":"2024","journal-title":"Front Immunol"},{"key":"2026090409012127300_bib52","doi-asserted-by":"publisher","first-page":"e0332026","DOI":"10.1371\/journal.pone.0332026","article-title":"Single-cell transcriptomic analysis reveals the association of Ccl6+Ccr2+Arg1+ macrophages with renal interstitial fibrosis in AKI","volume":"20","author":"Zheng","year":"2025","journal-title":"PLoS One"},{"key":"2026090409012127300_bib53","doi-asserted-by":"publisher","first-page":"3412","DOI":"10.7150\/ijbs.92447","article-title":"Molecular interaction of soluble Klotho with FGF23 in the pathobiology of aortic valve lesions induced by chronic kidney disease","volume":"20","author":"The","year":"2024","journal-title":"Int J Biol Sci"},{"key":"2026090409012127300_bib54","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/s12882-023-03125-1","article-title":"A potential link between fibroblast growth factor-23 and the progression of AKI to CKD","volume":"24","author":"Lu","year":"2023","journal-title":"BMC Nephrol"},{"key":"2026090409012127300_bib55","doi-asserted-by":"publisher","first-page":"2623","DOI":"10.1007\/s11255-024-03989-8","article-title":"The role of PI3K\/Akt signaling pathway in chronic kidney disease","volume":"56","author":"Wang","year":"2024","journal-title":"Int Urol Nephrol"},{"key":"2026090409012127300_bib56","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1007\/s10528-024-10756-y","article-title":"Wnt\/\u03b2-catenin pathway aggravates renal fibrosis by activating PUM2 transcription to repress YME1L-mediated mitochondrial homeostasis","volume":"63","author":"Song","year":"2025","journal-title":"Biochem Genet"},{"key":"2026090409012127300_bib57","doi-asserted-by":"publisher","first-page":"3152","DOI":"10.1111\/bph.15734","article-title":"The mineralocorticoid receptor in chronic kidney disease","volume":"179","author":"Barrera-Chimal","year":"2022","journal-title":"Br J Pharmacol"},{"key":"2026090409012127300_bib58","doi-asserted-by":"publisher","first-page":"e152330","DOI":"10.1172\/jci.insight.152330","article-title":"Mechanosensitive Piezo1 channels mediate renal fibrosis","volume":"7","author":"Zhao","year":"2022","journal-title":"JCI Insight"},{"key":"2026090409012127300_bib59","doi-asserted-by":"publisher","first-page":"1270979","DOI":"10.3389\/fmolb.2023.1270979","article-title":"Mechanotransductive receptor Piezo1 as a promising target in the treatment of fibrosis diseases","volume":"10","author":"Xu","year":"2023","journal-title":"Front Mol Biosci"},{"key":"2026090409012127300_bib60","doi-asserted-by":"publisher","first-page":"741060","DOI":"10.3389\/fcell.2021.741060","article-title":"Targeting mechanosensitive Piezo1 alleviated renal fibrosis through p38MAPK-YAP pathway","volume":"9","author":"Fu","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2026090409012127300_bib61","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1093\/ndt\/gfaa301","article-title":"Fibrosis and cancer: shared features and mechanisms suggest common targeted therapeutic approaches","volume":"37","author":"Landolt","year":"2022","journal-title":"Nephrol Dial Transplant"},{"key":"2026090409012127300_bib62","doi-asserted-by":"publisher","first-page":"e23005","DOI":"10.1096\/fj.202201870R","article-title":"Myocardin-related transcription factor contributes to renal fibrosis through the regulation of extracellular microenvironment surrounding fibroblasts","volume":"37","author":"Yamamura","year":"2023","journal-title":"FASEB J"},{"key":"2026090409012127300_bib63","doi-asserted-by":"publisher","first-page":"10832","DOI":"10.1073\/pnas.1910650117","article-title":"Matrix-transmitted paratensile signaling enables myofibroblast\u2013fibroblast cross talk in fibrosis expansion","volume":"117","author":"Liu","year":"2020","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026090409012127300_bib64","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1038\/s12276-023-00990-6","article-title":"An MRTF-A\u2013ZEB1\u2013IRF9 axis contributes to fibroblast\u2013myofibroblast transition and renal fibrosis","volume":"55","author":"Zhao","year":"2023","journal-title":"Exp Mol Med"},{"key":"2026090409012127300_bib65","doi-asserted-by":"publisher","first-page":"6040","DOI":"10.3390\/ijms22116040","article-title":"Basic biology and role in kidney disease","volume":"22","author":"Miranda","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2026090409012127300_bib66","doi-asserted-by":"publisher","first-page":"16364","DOI":"10.1074\/jbc.RA118.004073","article-title":"Yap\/Taz mediates mTORC2-stimulated fibroblast activation and kidney fibrosis","volume":"293","author":"Gui","year":"2018","journal-title":"J Biol Chem"},{"key":"2026090409012127300_bib67","doi-asserted-by":"publisher","first-page":"eadq3852","DOI":"10.1126\/scitranslmed.adq3852","article-title":"Podocyte YAP and TAZ hyperactivation drives glomerular epithelial proliferative diseases in mice and humans","volume":"17","author":"He","year":"2025","journal-title":"Sci Transl Med"},{"key":"2026090409012127300_bib68","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1042\/CS20245219","article-title":"Glycogen synthase kinase 3\u03b2: a key player in progressive chronic kidney disease","volume":"139","author":"Zhang","year":"2025","journal-title":"Clin Sci"},{"key":"2026090409012127300_bib69","doi-asserted-by":"publisher","first-page":"114186","DOI":"10.1016\/j.yexcr.2024.114186","article-title":"Targeting alternative splicing of fibronectin in human renal proximal tubule epithelial cells with antisense oligonucleotides to reduce EDA+ fibronectin production and block an autocrine loop that drives renal fibrosis","volume":"442","author":"Phanish","year":"2024","journal-title":"Exp Cell Res"},{"key":"2026090409012127300_bib70","doi-asserted-by":"publisher","first-page":"e1359","DOI":"10.1002\/ctm2.1359","article-title":"Genetic and pharmacological inhibition of METTL3 alleviates renal fibrosis by reducing EVL m6A modification through an IGF2BP2-dependent mechanism","volume":"13","author":"Ni","year":"2023","journal-title":"Clin Transl Med"},{"key":"2026090409012127300_bib71","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s13020-024-01004-x","article-title":"Metabolic reprogramming and renal fibrosis: what role might Chinese medicine play?","volume":"19","author":"Wang","year":"2024","journal-title":"Chin Med"},{"key":"2026090409012127300_bib72","doi-asserted-by":"publisher","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":"2026090409012127300_bib73","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1093\/jpp\/rgad032","article-title":"Patchouli alcohol against renal fibrosis of spontaneously hypertensive rats via Ras\/Raf-1\/ERK1\/2 signalling pathway","volume":"75","author":"Li","year":"2023","journal-title":"J Pharm Pharmacol"},{"key":"2026090409012127300_bib74","doi-asserted-by":"publisher","first-page":"2408753","DOI":"10.1002\/advs.202408753","article-title":"Deletion of pyruvate carboxylase in tubular epithelial cell promotes renal fibrosis by regulating SQOR\/cGAS\/STING-mediated glycolysis","volume":"12","author":"Huang","year":"2025","journal-title":"Adv Sci"},{"key":"2026090409012127300_bib75","doi-asserted-by":"publisher","first-page":"2534493","DOI":"10.1080\/0886022X.2025.2534493","article-title":"Urinary long non-coding RNA GAS5 as a noninvasive diagnostic biomarker for renal fibrosis","volume":"47","author":"Yu","year":"2025","journal-title":"Ren Fail"},{"key":"2026090409012127300_bib76","doi-asserted-by":"publisher","first-page":"113880","DOI":"10.1016\/j.intimp.2024.113880","article-title":"Adipose mesenchymal stem cell-derived extracellular vesicles alleviate renal fibrosis by reducing epithelial-mesenchymal transition via the FOXS1\/Wnt\/\u03b2-catenin signaling pathway","volume":"146","author":"Sun","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"2026090409012127300_bib77","doi-asserted-by":"publisher","first-page":"19","DOI":"10.4239\/wjd.v12.i1.19","article-title":"Metformin regulates inflammation and fibrosis in diabetic kidney disease through TNC\/TLR4\/NF-\u03baB\/miR-155-5p inflammatory loop","volume":"12","author":"Zhou","year":"2021","journal-title":"World J Diabetes"},{"key":"2026090409012127300_bib78","doi-asserted-by":"publisher","first-page":"3200","DOI":"10.1038\/s41467-024-47315-3","article-title":"Inhibition of ACSS2-mediated histone crotonylation alleviates kidney fibrosis via IL-1\u03b2-dependent macrophage activation and tubular cell senescence","volume":"15","author":"Li","year":"2024","journal-title":"Nat Commun"},{"key":"2026090409012127300_bib79","doi-asserted-by":"publisher","first-page":"2343817","DOI":"10.1080\/0886022X.2024.2343817","article-title":"DKK3 promotes renal fibrosis by increasing MFF-mediated mitochondrial dysfunction in Wnt\/\u03b2-catenin pathway-dependent manner","volume":"46","author":"Song","year":"2024","journal-title":"Ren Fail"},{"key":"2026090409012127300_bib80","doi-asserted-by":"publisher","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":"2026090409012127300_bib81","doi-asserted-by":"publisher","first-page":"139842","DOI":"10.1016\/j.ijbiomac.2025.139842","article-title":"Identification of key antifibrotic targets FPR1, TAS2R5, and LRP2BP of valsartan in diabetic nephropathy: a transcriptomics-driven study integrating machine learning, molecular docking, and dynamics simulations","volume":"297","author":"Wang","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"2026090409012127300_bib82","doi-asserted-by":"publisher","first-page":"156738","DOI":"10.1016\/j.phymed.2025.156738","article-title":"Diosmin attenuates UUO-induced renal ferroptosis and fibrosis by inhibiting the HIF-1\u03b1\/FABP4 signaling axis","volume":"141","author":"Zhao","year":"2025","journal-title":"Phytomedicine"},{"key":"2026090409012127300_bib83","doi-asserted-by":"publisher","first-page":"2403230","DOI":"10.1002\/adhm.202403230","article-title":"Kidney fibrosis in vitro and in vivo models: path toward physiologically relevant humanized models","volume":"14","author":"Addario","year":"2025","journal-title":"Adv Healthc Mater"},{"key":"2026090409012127300_bib84","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1093\/ndt\/gfac143","article-title":"End-to-end interstitial fibrosis assessment of kidney biopsies with a machine learning-based model","volume":"37","author":"Liu","year":"2022","journal-title":"Nephrol Dial Transplant"},{"key":"2026090409012127300_bib85","doi-asserted-by":"publisher","first-page":"101712","DOI":"10.1016\/j.molmet.2023.101712","article-title":"Calponin 2 harnesses metabolic reprogramming to determine kidney fibrosis","volume":"71","author":"Gui","year":"2023","journal-title":"Mol Metab"},{"key":"2026090409012127300_bib86","doi-asserted-by":"crossref","first-page":"e03287","DOI":"10.1002\/adhm.202503287","article-title":"Development of a synthetic 3D platform for compartmentalized kidney in vitro disease modeling","volume":"15","author":"M\u00f6hl","year":"2026","journal-title":"Adv Healthc Mater"},{"key":"2026090409012127300_bib87","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/978-1-0716-1382-5","article-title":"Methods for the study of renal fibrosis in human pluripotent stem cell-derived kidney organoids","volume":"2299","author":"Moran-Horowich","year":"2021","journal-title":"Methods Mol Biol"},{"key":"2026090409012127300_bib88","doi-asserted-by":"publisher","first-page":"e2400807","DOI":"10.1002\/adhm.202400807","article-title":"3D humanized bioprinted tubulointerstitium model to emulate renal fibrosis in vitro","volume":"13","author":"Addario","year":"2024","journal-title":"Adv Healthc Mater"},{"key":"2026090409012127300_bib89","doi-asserted-by":"publisher","first-page":"17509","DOI":"10.1038\/s41598-025-02383-3","article-title":"Neutrophil extracellular traps aggravate uremic cardiomyopathy by inducing myocardial fibroblast pyroptosis","volume":"15","author":"Xu","year":"2025","journal-title":"Sci Rep"},{"key":"2026090409012127300_bib90","doi-asserted-by":"publisher","first-page":"1161036","DOI":"10.3389\/fmolb.2023.1161036","article-title":"Impact of renal tubular Cpt1a overexpression on the kidney metabolome in the folic acid-induced fibrosis mouse model","volume":"10","author":"Cuevas-Delgado","year":"2023","journal-title":"Front Mol Biosci"},{"key":"2026090409012127300_bib91","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/5521051","article-title":"Deficiency of IKK\u03b1 in macrophages mitigates fibrosis progression in the kidney after renal ischemia-reperfusion injury","volume":"2021","author":"Zhang","year":"2021","journal-title":"J Immunol Res"},{"key":"2026090409012127300_bib92","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1159\/000519495","article-title":"Pirfenidone attenuates renal tubulointerstitial fibrosis through inhibiting miR-21","volume":"146","author":"Bi","year":"2022","journal-title":"Nephron"},{"key":"2026090409012127300_bib93","doi-asserted-by":"publisher","first-page":"2444393","DOI":"10.1080\/0886022X.2024.2444393","article-title":"Curcumin alleviates renal fibrosis in chronic kidney disease by targeting the circ_0008925-related pathway","volume":"47","author":"An","year":"2025","journal-title":"Ren Fail"},{"key":"2026090409012127300_bib94","doi-asserted-by":"publisher","first-page":"102894","DOI":"10.1016\/j.jaut.2022.102894","article-title":"SB431542 alleviates lupus nephritis by regulating B cells and inhibiting the TLR9\/TGF\u03b21\/PDGFB signaling","volume":"132","author":"Xia","year":"2022","journal-title":"J Autoimmun"},{"key":"2026090409012127300_bib95","doi-asserted-by":"publisher","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":"2026090409012127300_bib96","doi-asserted-by":"crossref","first-page":"14265","DOI":"10.3390\/ijms232214265","article-title":"Transforming growth factor \u03b21 overexpression is associated with insulin resistance and rapidly progressive kidney fibrosis under diabetic conditions","volume":"23","author":"VF","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026090409012127300_bib97","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s13287-025-04226-4","article-title":"Mesenchymal cell-derived exosomes and miR-29a-3p mitigate renal fibrosis and vascular rarefaction after renal ischemia reperfusion injury","volume":"16","author":"Huang","year":"2025","journal-title":"Stem Cell Res Ther"},{"key":"2026090409012127300_bib98","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1038\/s41401-024-01298-5","article-title":"Mitochondrial calcium uniporter promotes kidney aging in mice through inducing mitochondrial calcium-mediated renal tubular cell senescence","volume":"45","author":"Xiong","year":"2024","journal-title":"Acta Pharmacol Sin"},{"key":"2026090409012127300_bib99","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.7150\/ijbs.93598","article-title":"Chk2 modulates Bmi1-deficiency-induced renal aging and fibrosis via oxidative stress, DNA damage, and p53\/TGF\u03b21-induced epithelial-mesenchymal transition","volume":"20","author":"Lu","year":"2024","journal-title":"Int J Biol Sci"},{"key":"2026090409012127300_bib100","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1159\/000521100","article-title":"Renal interstitial fibrosis is reduced in high-fat diet-induced obese pigs following renal denervation from the intima and adventitia of the renal artery","volume":"47","author":"Zhu","year":"2022","journal-title":"Kidney Blood Press Res"},{"key":"2026090409012127300_bib101","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1097\/ALN.0000000000005452","article-title":"Persistent renal hypoxia and histologic changes at 4 weeks after cardiopulmonary bypass in sheep","volume":"142","author":"Furukawa","year":"2025","journal-title":"Anesthesiology"},{"key":"2026090409012127300_bib102","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1002\/ame2.12185","article-title":"Development of a unilateral ureteral obstruction model in cynomolgus monkeys","volume":"4","author":"Huang","year":"2021","journal-title":"Anim Models Exp Med"},{"key":"2026090409012127300_bib103","doi-asserted-by":"publisher","first-page":"110289","DOI":"10.1016\/j.cbi.2022.110289","article-title":"Transforming growth factor-\u03b2 signaling: from tissue fibrosis to therapeutic opportunities","volume":"369","author":"Ren","year":"2023","journal-title":"Chem Biol Interact"},{"key":"2026090409012127300_bib104","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1053\/j.ajkd.2021.11.010","article-title":"Antifibrotic agents for the management of CKD: a review","volume":"80","author":"Ruiz-Ortega","year":"2022","journal-title":"Am J Kidney Dis"},{"key":"2026090409012127300_bib105","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.34067\/KID.0003782020","article-title":"mTOR signaling in kidney diseases","volume":"1","author":"Gui","year":"2020","journal-title":"Kidney360"},{"key":"2026090409012127300_bib106","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s00018-025-05688-8","article-title":"SGLT2 inhibitor empagliflozin ameliorates tubulointerstitial fibrosis in DKD by downregulating renal tubular PKM2","volume":"82","author":"Cai","year":"2025","journal-title":"Cell Mol Life Sci"},{"key":"2026090409012127300_bib107","doi-asserted-by":"publisher","first-page":"102946","DOI":"10.1016\/j.redox.2023.102946","article-title":"Non-steroidal mineralocorticoid receptor antagonist finerenone ameliorates mitochondrial dysfunction via PI3K\/Akt\/eNOS signaling pathway in diabetic tubulopathy","volume":"68","author":"Yao","year":"2023","journal-title":"Redox Biol"},{"key":"2026090409012127300_bib108","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1080\/10985549.2023.2253130","article-title":"Module 4-deficient CCN2\/connective tissue growth factor attenuates the progression of renal fibrosis via suppression of focal adhesion kinase phosphorylation in tubular epithelial cells","volume":"43","author":"Amano","year":"2023","journal-title":"Mol Cell Biol"},{"key":"2026090409012127300_bib109","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1016\/j.stem.2025.07.014","article-title":"Targeting ECM-producing cells with CAR-T therapy alleviates fibrosis in chronic kidney disease","volume":"32","author":"Zhao","year":"2025","journal-title":"Cell Stem Cell"},{"key":"2026090409012127300_bib110","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.nefro.2023.09.001","article-title":"Losartan ameliorates renal fibrosis by inhibiting tumor necrosis factor signal pathway","volume":"44","author":"Wang","year":"2024","journal-title":"Nefrolog\u00eda"},{"key":"2026090409012127300_bib111","doi-asserted-by":"crossref","first-page":"sfae394","DOI":"10.1093\/ckj\/sfae394","article-title":"First real-world evidence of sparsentan efficacy in patients with IgA nephropathy treated with SGLT2 inhibitors","volume":"18","author":"Schanz","year":"2024","journal-title":"Clin Kidney J"},{"key":"2026090409012127300_bib112","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1093\/ndt\/gfae021","article-title":"Sparsentan is superior to losartan in the gddY mouse model of IgA nephropathy","volume":"39","author":"Nagasawa","year":"2024","journal-title":"Nephrol Dial Transplant"},{"key":"2026090409012127300_bib113","doi-asserted-by":"publisher","DOI":"10.1101\/2025.08.25.672225","article-title":"Pirfenidone treatment attenuates fibrosis in autosomal dominant polycystic kidney disease","author":"Remadevi","journal-title":"bioRxiv"},{"key":"2026090409012127300_bib114","doi-asserted-by":"publisher","first-page":"2088","DOI":"10.3390\/ijms25042088","article-title":"Long-term effects of tolvaptan in autosomal dominant polycystic kidney disease: predictors of treatment response and safety over 6 years of continuous therapy","volume":"25","author":"Yamazaki","year":"2024","journal-title":"Int J Mol Sci"},{"key":"2026090409012127300_bib115","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S2213-8587(21)00242-4","article-title":"Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial","volume":"9","author":"Heerspink","year":"2021","journal-title":"The Lancet. Lancet Diabetes Endocrinol"},{"key":"2026090409012127300_bib116","doi-asserted-by":"publisher","first-page":"2555685","DOI":"10.1080\/0886022X.2025.2555685","article-title":"Non-invasive assessment techniques for renal fibrosis: advances and perspectives","volume":"47","author":"Tang","year":"2025","journal-title":"Ren Fail"},{"key":"2026090409012127300_bib117","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1186\/s13287-025-04567-0","article-title":"iPSC-based drug discovery identified the Hippo signaling pathway as a therapeutic target in the fibrosis of NPHP1-deficient nephronophthisis","volume":"16","author":"Suzuki","year":"2025","journal-title":"Stem Cell Res Ther"}],"container-title":["Clinical Kidney Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ckj\/advance-article-pdf\/doi\/10.1093\/ckj\/sfag275\/70619137\/sfag275.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/19\/9\/sfag275\/70619137\/sfag275.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/19\/9\/sfag275\/70619137\/sfag275.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:01:29Z","timestamp":1788526889000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ckj\/article\/doi\/10.1093\/ckj\/sfag275\/8759698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":117,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ckj\/sfag275","relation":{},"ISSN":["2048-8505","2048-8513"],"issn-type":[{"value":"2048-8505","type":"print"},{"value":"2048-8513","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9]]},"published":{"date-parts":[[2026,8,12]]},"article-number":"sfag275"}}