CIDEC silencing attenuates diabetic nephropathy via inhibiting apoptosis and promoting autophagy

• Main Authors: Gao‐shu Zheng, Yan‐min Tan, Yuan‐yuan Shang, Ya‐peng Liu, Bo‐ang Hu, Di Wang, Lu Han, Zhi‐hao Wang, Wei Zhang, Yun Ti, Ming Zhong
• Format: Article
• Language: English
• Published: Wiley 2021-08-01
• Series: Journal of Diabetes Investigation
• Subjects: CIDEC; Diabetic nephropathy
• Online Access: https://doi.org/10.1111/jdi.13534

Abstract Objective The role of cell death‐inducing DFF45‐like effector C (CIDEC) in insulin resistance has been established, and it is considered to be an important trigger factor for the progression of diabetic nephropathy (DN). We intend to explore whether CIDEC plays an important role in the regulation of DN and its potential mechanism. Methods High‐fat diet and low dose streptozotocin were used to establish type 2 diabetic rat model. We investigate the role of CIDEC in the pathogenesis and process of DN through histopathological analysis, western blot and gene silencing. Meanwhile, the effect of CIDEC on renal tubular epithelial cells stimulated by high glucose was also verified. Results DM group exhibited glucose and lipid metabolic disturbance, with hypertrophy of kidneys, damaged renal function, increased apoptosis, decreased autophagy, glomerulosclerosis and interstitial fibrosis. CIDEC gene silencing improved metabolic disorder and insulin resistance, alleviated renal hypertrophy and renal function damage, decreased glomerular and tubular apoptosis, increased autophagy and inhibited renal fibrosis. At the cellular level, high glucose stimulation increased CIDEC expression in renal tubular epithelial cells, accompanied by increased apoptosis and decreased autophagy. CIDEC gene silencing can improve autophagy and reduce apoptosis. At the molecular level, CIDEC gene silencing also decreased the expression of early growth response factor (EGR)1 and increased the expression of adipose triglyceride lipase (ATGL). Conclusion CIDEC gene silencing may delay the progression of DN by restoring autophagy activity and inhibiting apoptosis with the participation of EGR1and ATGL.