HNF3α Targets Nckap1l and Promotes Renal Fibrosis Following Ischemia‐Reperfusion Injury

• DOI: 10.1002/advs.202410764
• Publication Date: 2025-03-17T08:44:18Z
• Authors: Ling Hou; Yan Guo; Shuang Xu; Mi Bai; Weidong Cao; Yue Zhang; Zhanjun Jia; Aihua Zhang
• Keywords: Renal ischemia

Abstract Chronic Kidney Disease (CKD) is a global health challenge, with acute kidney injury (AKI) from ischemia‐reperfusion (IRI) as common cause. This study explored the role of Hepatocyte Nuclear Factor 3 alpha (HNF3α/FOXA1) in renal fibrosis and CKD after IRI. biopsy specimens patients mouse models (IRI or unilateral ureteral obstruction) showed HNF3α upregulation fibrotic kidneys, linked to function decline. Additional experiments demonstrated that deletion mitigated IRI‐induced fibrosis, overexpression led increased fibrosis. Examination potential mechanism by transcriptome sequencing CUT&Tag suggested promoted increasing expression NCK associated protein 1 like (Nckap1l, formerly known hematopoietic [Hem1]), vital component WAVE complex which plays significant cytoskeletal regulation cell migration. These results underscore critical following IRI, also identify Nckap1l therapeutic target, thus opening new avenues for research interventions