CERS6-derived ceramides aggravate kidney fibrosis by inhibiting PINK1-mediated mitophagy in diabetic kidney disease
Xiangyu Wang, Minkai Song, Xiaomin Li, Cailin Su, Yanlin Yang, Kai Wang, Cuiting Liu, Zongji Zheng, Yijie Jia, Shijing Ren, Wenhui Dong, Jiaqi Chen, Ting Wang, Lerong Liu, Meiping Guan, Chao Zhang, Yaoming Xue
Abstract
This article addresses the roles of ceramide synthase 6 ( CERS6) and CERS6-derived ceramides in renal tubular epithelial cells of diabetic kidney disease (DKD) associated interstitial fibrosis. Results from knockdown of CERS6 adjusted the ceramide pool in kidney cortex and markedly protected from diabetic-induced kidney fibrosis in vivo and in vitro. Mechanically, CERS6-derived ceramides might interact with PINK1 to inhibit PINK1/Parkin-mediated mitophagy and aggravate renal interstitial fibrosis in DKD.
Topics & Concepts
MitophagyCeramideCeramide synthasePINK1Renal cortexKidneyKidney diseaseMedicineFibrosisMitochondrionInternal medicineGene knockdownEndocrinologyCancer researchBiologyCell biologyApoptosisAutophagyBiochemistrySphingolipid Metabolism and SignalingPancreatic function and diabetesAutophagy in Disease and Therapy