{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:00:37Z","timestamp":1791655237449,"version":"4.3.4"},"reference-count":33,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300846"],"award-info":[{"award-number":["82300846"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170708"],"award-info":[{"award-number":["82170708"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Maladaptive repair following acute kidney injury (AKI) is an independent risk factor for the progression to chronic kidney disease (CKD). We hypothesize that renal tubular cell senescence and subsequent epithelial\u2010mesenchymal transition drive maladaptive repair after AKI, ultimately leading to chronic renal fibrosis. We re\u2010analyzed single\u2010cell RNA sequencing data (ScRNA\u2010seq, GSE212273) from kidney tissues post\u2010IRI. In\u00a0vivo, we employed unilateral IRI and folic acid models to simulate the AKI to CKD transition. Senolytics or verteporfin were given from Day 3 post\u2010modeling. In\u00a0vitro, human renal tubular epithelial (HK\u20102) cells were exposed to hydrogen peroxide or TGF\u2010\u03b2. Sustained YAP1 overexpression promoted fibroblast activation and a profibrotic phenotypic shift. AKI induced a sustained increase in YAP1 expression, which was associated with tubular cell senescence and renal interstitial fibrosis. Senolytics effectively suppressed YAP1 activity, renal senescence, and alleviated kidney fibrosis. In\u00a0vitro, persistent oxidative stress upregulated YAP1 expression and induced cell senescence. Knockdown of YAP1 downregulated Hippo signaling pathway, extracellular matrix reorganization, and reduced cell senescence. Conversely, YAP1 overexpression reversed the anti\u2010senescence effect of senolytics. Finally, pharmacological inhibition of YAP1\/TEAD1 attenuated cell senescence and post\u2010ischemic renal fibrosis. Our findings indicate that sustained YAP1 overexpression mediates tubular cell senescence, which drives maladaptive kidney repair and facilitates the AKI to CKD transition. Senolytics or verteporfin therapy initiated after the peak of AKI offers a dual benefit: it protects the regenerative capacity of tubular cells and concurrently inhibits YAP1\u2010driven epithelial\u2010mesenchymal transition, thereby mitigating the progression of renal fibrosis.<\/jats:p>","DOI":"10.1096\/fj.202503969rr","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:55:49Z","timestamp":1782906949000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting\n                    <scp>YAP1<\/scp>\n                    \u2010Mediated Tubular Cell Senescence to Attenuate Maladaptive Repair and Fibrotic Transition After Acute Kidney Injury"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9667-8645","authenticated-orcid":false,"given":"Zhibo","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Nephrology Shanxi Provincial People's Hospital, The Fifth Clinical Medical College of Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiping","family":"An","sequence":"additional","affiliation":[{"name":"Shanxi Provincial People's Hospital Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghou","family":"Sang","sequence":"additional","affiliation":[{"name":"Shanxi Provincial People's Hospital Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanxi Provincial People's Hospital Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxiu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shanxi Provincial People's Hospital Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanxi Provincial People's Hospital Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nephrology Shanxi Provincial People's Hospital, The Fifth Clinical Medical College of Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshuang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shanxi Provincial People's Hospital The Fifth Clinical Medical College of Shanxi Medical University, Shanxi Provincial Key Laboratory of Kidney Disease  Taiyuan China"},{"name":"Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.23876\/j.krcp.2018.37.3.185"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2019.02.006"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000067652.51441.21"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33110-5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3458"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01544-2023"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2281156"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1681\/01.asn.0000926916.36548.91"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25094610"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw9886"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00565-16"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.03.038"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000840"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000000000024"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20943823"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2009.03.011"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149489"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/867140"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.11.028"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-024-01045-4"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.07920713"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.20"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2015.3"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215518"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090517"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100629108"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2144"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2012.04.001"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.01.006"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010020205"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00475.2013"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202503969RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202503969RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202503969RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T14:08:38Z","timestamp":1784815718000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202503969RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":33,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2026,7,15]]}},"alternative-id":["10.1096\/fj.202503969RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202503969rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"assertion":[{"value":"2025-10-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72104"}}