{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:30:12Z","timestamp":1787157012542,"version":"build-2736575974"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"\n Background:<\/jats:title>\n Maladaptive repair following acute kidney injury leads to CKD, but the underlying molecular drivers remain incompletely understood. Kr\u00fcppel-like factor 5 (Klf5), a zinc finger transcription factor, is upregulated in kidney diseases. However, its role and regulation in post-injury kidney repair are unknown.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n Klf5 expression was analyzed in C57BL\/6 mice after unilateral ischemia\/reperfusion (I\/R), repeated low-dose cisplatin (RLDC), and unilateral ureteral obstruction (UUO) in vivo, in human CKD biopsies, and in TGF\u03b2-, TNF\u03b1, and RLDC-treated kidney proximal tubule cells in vitro. The role of Klf5 was investigated using\n Klf5<\/jats:italic>\n knockdown proximal tubular cells in vitro and proximal tubule-specific\n Klf5<\/jats:italic>\n knockout mouse model in vivo. To examine the regulation by nuclear factor-\u03baB (NF-\u03baB), p65 (RelA, a key component of the NF-\u03baB complex) was specifically ablated from kidney proximal tubule cells in mice.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Klf5 was transcriptionally induced in renal proximal tubular cells in mouse models of maladaptive kidney repair and in human CKD biopsies. Proximal tubule-specific\n Klf5<\/jats:italic>\n knockout significantly reduced fibrosis, inflammation, dedifferentiation, and cellular senescence in post-injury kidneys, leading to improved kidney repair. Genetic or pharmacologic inhibition of NF-\u03baB attenuated Klf5 expression and downstream fibrotic and inflammatory responses. NF-\u03baB was further proved to transactivate Klf5 via promoter binding.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n The results demonstrated Klf5 as a critical mediator of maladaptive repair and CKD development after AKI. Mechanistically, Klf5 was transcriptionally up-regulated via NF-\u03baB. Upon induction, Klf5 contributed to renal inflammation, senescence, and fibrosis, highlighting potential therapeutic targets.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000001219","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:00:45Z","timestamp":1787155245000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Klf5 Is Upregulated via NF-kB to Promote Maladaptive Kidney Repair and CKD Progression"],"prefix":"10.1681","author":[{"given":"Zhengwei","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6426-357X","authenticated-orcid":false,"given":"Xiaoru","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital of Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2203-3917","authenticated-orcid":false,"given":"Santhakumar","family":"Manicassamy","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Medical College of Georgia at Augusta University, Augusta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9087-2085","authenticated-orcid":false,"given":"Hui","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Medicine, Renal Division, Emory University School of Medicine, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3538-8095","authenticated-orcid":false,"given":"Zheng","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,8,19]]},"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001219","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:00:46Z","timestamp":1787155246000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1681\/asn.0000001219","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]},"assertion":[{"value":"2025-09-02","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-03","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}