HNF3α Targets Nckap1l and Promotes Renal Fibrosis Following Ischemia-Reperfusion Injury.

ABSTRACT: Chronic Kidney Disease (CKD) is a global health challenge, with acute kidney injury (AKI) from ischemia-reperfusion injury (IRI) as a common cause. This study explored the role of Hepatocyte Nuclear Factor 3 alpha (HNF3α/FOXA1) in renal fibrosis and CKD after IRI. Kidney biopsy specimens from CKD patients and mouse models (IRI or unilateral ureteral obstruction) showed HNF3α upregulation in fibrotic kidneys, linked to renal function decline. Additional experiments demonstrated that deletion of HNF3α mitigated IRI-induced renal fibrosis, and that overexpression of HNF3α led to increased fibrosis. Examination of the potential mechanism by transcriptome sequencing and CUT&Tag sequencing suggested that HNF3α promoted renal fibrosis by increasing the expression of the NCK associated protein 1 l

SUBMITTER: Hou L 

PROVIDER: S-EPMC12097113 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature