Sodium-glucose cotransporter 2 inhibitors ameliorate glutathione cysteine ligase modifier-mediated oxidative stress and subsequent ferroptosis in proximal tubules of diabetic kidney disease.

ABSTRACT:

Objectives

Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease. The precise molecular mechanism of ferroptosis, an iron-dependent and non-apoptotic form of regulated cell death, remains poorly understood in DKD, as does the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on ferroptosis-mediated DKD.

Methods

This study used bulk RNA sequencing, in vitro and in vivo models, and human kidney samples to explore the molecular mechanisms involved in oxidative stress and ferroptosis in the proximal tubule (PT) of DKD.

Results

High glucose (HG) induced features of ferroptosis in HK-2 cells. Transcriptome analysis of primary PT cells from diabetic patients indicated that glutathione cysteine ligase modifier (GCLM) subunit is involved in ferr

SUBMITTER: Tsai YC 

PROVIDER: S-EPMC12308872 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature