CIDEC silencing attenuates diabetic nephropathy via inhibiting apoptosis and promoting autophagy

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.

Protective Effects of Glycyrrhiza Total Flavones on Liver Injury Induced by Streptococcus agalactiae in Tilapia (Oreochromis niloticus)

“…Li et al have reported that cidec plays an important role in lipid metabolism, and abnormal cidec expression can lead to lipid metabolism disorders [ 52 ]. The function of cidec was also reported by foreign scholars, and it was found that cidec expression induced the apoptosis process of cells [ 53 ]. In this study, the expression of cidec and cideb genes was significantly down-regulated, indicating that Streptococcus affected the expression of the cide family in liver tissue, resulting in abnormal liver metabolic function and further liver tissue injury.…”

Exosomes as nanostructures deliver miR-204 in alleviation of mitochondrial dysfunction in diabetic nephropathy through suppressing methyltransferase-like 7A-mediated CIDEC N6-methyladenosine methylation

“…CIDEC is a key factor in insulin resistance, and its silencing has been linked to the prevention of DN progression [ 31 ]. To determine whether there is an interaction between METTL7A and CIDEC in DN, HG-induced HK-2 cells were transfected with si-METTL7A.…”

“…Previous research showed that CIDEC deficiency could mitigate pulmonary vascular remodeling in type 2 diabetes rat models [ 30 ]. A recent study has shown that CIDEC knockdown can ameliorate metabolic abnormalities, insulin resistance, and renal impairment, suppress cell apoptosis and renal fibrosis, and enhance autophagy to prevent DN progression [ 31 ]. Despite little knowledge of the relationship between methyltransferases and CIDEC, evidence has shown that METTL7A also plays a vital role in cell apoptosis and survival [ 32 ].…”

Microarray expression profile of exosomal circRNAs from high glucose stimulated human renal tubular epithelial cells

“…High glucose promoted apoptosis and inhibited autophagy of renal tubular epithelial cells with increasing cell death-inducing DFF45-like effector C expression. Inhibiting apoptosis may delay the progression of DN [47] . In addition, the therapeutic effects of zinc supplementation in DN were regulated by increasing hexokinase II expression and the preservation glucose-metabolism-related pathways [48] .…”