AUTHOR=Wang Yi-Fan , Zheng Dan , Zhang Ying , Li Xiao-Fen , Xia Ming , Tang Hai-Ming , Huang Chun-Hua , Li Mao-Juan , Lou Di-Dong 

TITLE=Renal tubular epithelial cell related partial epithelial-mesenchymal transition in AAⅠ induced renal fibrosis via Wnt7b/β-catenin signaling

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1571960

DOI=10.3389/fphar.2025.1571960

ISSN=1663-9812

ABSTRACT=IntroductionThis study investigates the pathological progressions in kidneys affected by aristolochic acid nephropathy (AAN) and explores the molecular mechanisms underlying the fibrotic process, specifically focusing on the Wnt7b/β-catenin signaling pathway.MethodsBoth mice and human kidney-2 (HK-2) cells were treated with aristolochic acid I (AAI). In mice, we monitored blood urea nitrogen (BUN), serum creatinine (Scr), kidney injury molecule-1 (KIM-1), pathological modifications of renal tubular epithelial cells (RTECs), and fibrosis degrees during acute/chronic disease phases. Wnt7b/β-catenin expression was evaluated through transcriptome analysis and laboratory assays (immunohistochemistry, Western blotting, immunoelectron microscopy) in acute AAN and cultured cells. Concurrent assays measured representative proteins: Aquaporin 1 (AQP1), Topoisomerase IIα (TOP2A), Vascular Cell Adhesion Molecule-1 (VCAM-1), and α-smooth muscle actin (α-SMA) in chronic AAN RTECs.ResultsAAI increased Scr, BUN, and KIM-1 levels by causing RTEC necrotic shedding in acute stages and promoted renal interstitial fibrosis chronically. Elevated Wnt7b pathway proteins enhanced damaged RTEC regeneration, with regenerated cells expressing mesenchymal proteins VCAM-1 and α-SMA.DiscussionThe Wnt7b/β-catenin signaling pathway connects acute tubule damage to fibrosis, explaining AAN’s pathological continuum. These findings clarify how acute injury progresses to chronic fibrosis in AAN.