关键词: 含杆状病毒IAP重复蛋白2, HIF-1α/BNIP3/mTOR通路, 糖尿病肾病, 系膜细胞, 自噬

Abstract: Objective To investigate the impacts of baculovirus IAP repeat containing protein 2 (BIRC2) on mesangial cell injury and autophagy in human diabetic nephropathy (DN) in vitro. Methods Human glomerular mesangial cells HGMCs were cultured routinely and randomly divided into control group, model group, sh NC group, BIRC2 shRNA group, and BIRC2 shRNA+YC-1 group(HIF-1α inhibitor YC-1, 25 μmol/L). CCK-8 method was applied to detect the activity of HGMCs. Flow cytometry was applied to detect cell apoptosis. ELISA method was applied to detect the levels of interleukin(IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) of cells in each group. Transmission electron microscopy was applied to observe the number of autophagosomes of cells in each group. Western blot was applied to detect the expression of BIRC2, HIF-1α/BNIP3/mTOR pathway related proteins and autophagy related protein Beclin-1, and microtubule-associated protein 1 light chain 3 (LC3) of cells in each group. Results Compared with the control group, the absorbance (A) value (48 h, 72 h), IL-1β, IL-6, TNF-α levels, BIRC2 protein expression, and mTOR phosphorylation levels of HGMCs in the model group were significantly increased(P＜0.05), the apoptosis rate of HGMCs, the number of autophagosomes, and the expression levels of HIF-1α, BNIP3, Beclin-1, and LC3 Ⅱ/Ⅰ proteins were significantly reduced (P＜0.05). Compared with the model group and sh NC group, the changes in the corresponding indicators of HGMCs in the BIRC2 shRNA group were opposite (P＜0.05). Conclusions Downregulation of BIRC2 expression alleviates the damage of mesangial cells in human diabetic nephropathy and promotes autophagy in vitro.

Key words: baculoviral IAP repeat containing protein 2(BIRC2), HIF-1α/BNIP3/mTOR pathway, diabetic nephropathy, mesangial cells, autophagy