CNPY2 Aggravates Renal Tubular Cell Ferroptosis in Diabetic Nephropathy by Regulating PERK/ATF4/CHAC1 Pathway and MAM Integrity.

ABSTRACT: Ferroptosis is emerging as a novel mechanism for understanding renal tubular injury in diabetic nephropathy (DN). The mitochondria-associated endoplasmic reticulum membrane (MAM) plays a crucial role in the regulation of numerous cellular processes, including mitochondrial dysfunction and endoplasmic reticulum (ER) stress (ERS). However, the exact mechanism underlying ferroptosis and MAM in DN remains unclear. In this study, we identified that canopy FGF signaling regulator 2 (CNPY2) is upregulated in the renal tubules of DN. Downregulation of CNPY2 alleviated ferroptosis and improved MAM integrity in the renal tubular epithelial cells of db/db mice. Conversely, CNPY2 overexpression aggravated tubular injury in DN by accelerating ferroptosis and disrupting MAM formation. Mechanistically, C

SUBMITTER: Chen J 

PROVIDER: S-EPMC12224942 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature