TCF3 downregulation alleviates renal fibrosis via PI3K/Akt/mTOR pathway inhibition and autophagy restoration in diabetic nephropathy.

ABSTRACT:

Background

Diabetic nephropathy (DN) is characterized by tubular injury and tubulointerstitial fibrosis, leading to progressive renal dysfunction. While dysregulation of autophagy has been linked to DN pathogenesis, the underlying regulatory mechanisms remain incompletely understood. This study aimed to test the hypothesis that transcription factor 3 (TCF3) serves as a critical upstream regulator of autophagy dysfunction in DN by suppressing Netrin-1 expression, thereby promoting epithelial-mesenchymal transition (EMT) through activation of the PI3K/Akt/mTOR pathway.

Methods

We established a DN rat model using high-fat diet followed by low-dose streptozotocin injection (25 mg/kg). Thirty-five male Sprague-Dawley rats were divided into five groups (n = 6-7/group, with

SUBMITTER: Liu CX 

PROVIDER: S-EPMC12702734 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature