High glucose induces apoptosis via upregulation of Bim expression in proximal tubule epithelial cells

Oncotarget
Xiao-Qian ZhangLin Liao

Abstract

Diabetic nephropathy is the primary cause of end-stage renal disease. Apoptosis of tubule epithelial cells is a major feature of diabetic nephropathy. The mechanisms of high glucose (HG) induced apoptosis are not fully understood. Here we demonstrated that, HG induced apoptosis via upregulating the expression of proapoptotic Bcl-2 homology domain 3 (BH3)-only protein Bim protein, but not bring a significant change in the baseline level of autophagy in HK2 cells. The increase of Bim expression was caused by the ugregulation of transcription factors, FOXO1 and FOXO3a. Bim expression initiates BAX/BAK-mediated mitochondria-dependent apoptosis. Silence of Bim by siRNA in HK2 cells prevented HG-induced apoptosis and also sensitized HK2 cells to autophagy during HG treatment. The autophagy inhibitor 3-MA increased the injury in Bim knockdown HK2 cells by retriggering apoptosis. The above results suggest a Bim-independent apoptosis pathway in HK2 cells, which normally could be inhibited by autophagy. Overall, our results indicate that HG induces apoptosis via up-regulation of Bim expression in proximal tubule epithelial cells.

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Citations

Apr 30, 2019·Journal of Cellular Physiology·Sugandh SaxenaPoonam Kakkar
May 5, 2018·Journal of Diabetes Research·Xuehai ChenHong Zhu
Jul 2, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Caigu HeYanfang Zheng

Related Concepts

3-methyladenine
BCL2-Related Protein 11
Adenine
Programmed Cell Death, Type II
Epithelial Cells
Anhydrous Dextrose
Kidney Tubules, Proximal
Apoptosis, Intrinsic Pathway
Gene Silencing
Short Hairpin RNA

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