Effect of Tasosartan on human renal tubular epithelial cells induced by glucose and oxygen deprivation and its mechanism
LIU Xiujuan1▲ WU Yu2 ZOU Xin1 YU Yanyan1 GENG Yanqiu3▲ SHUANG Feng4
1.Department of Nephrology, 908 Hospital of People’s Liberation Army Joint Logistic Support Forces, Jiangxi Province, Nanchang 330002, China;
2.Clinical Laboratory, 908 Hospital of People’s Liberation Army Joint Logistic Support Forces, Jiangxi Province, Nanchang 330002, China;
3.Department of Nephrology, the Third Medical Center of People’s Liberation Army General Hospital, Beijing 100039, China;
4.Department of Orthopedics, 908 Hospital of People’s Liberation Army Joint Logistic Support Forces, Jiangxi Province, Nanchang 330002, China
Abstract Objective To investigate the effect of Tasosartan on human renal tubular epithelial cells (HK-2) induced by glucose and oxygen deprivation and its mechanism. Methods HK-2 cells were divided into control group (normal culture), glucose and oxygen deprivation group (glucose and oxygen deprivation culture) and Tasosartan group (glucose and oxygen deprivation cells were cultured with Tasosartan). MTT assay was used to detect cell proliferation, flow cytometry was used to detect cell apoptosis, Western blot analysis of α-smooth muscle actin (α-SMA), type Ⅰ collagen (Col Ⅰ), fibronectin (Fibronectin), E-cadherin (E-cadherin), glucose-regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP), and toll-like receptor 4 (TLR4); meanwhile, the effect of TLR4 overexpression on HK-2 cells was detected. Results The cell proliferation rate in 15 μmol/L Tasosartan group was lower than that in glucose and oxygen deprivation group (P < 0.05). 10 μmol/L Tasosartan was selected as the concentration of glucose and oxygen deprivation HK-2 cells. The apoptosis rate of Tasosartan group was lower than that of glucose and oxygen deprivation group, the protein expression of α-SMA, Col Ⅰ and Fibronectin was lower than that of glucose and oxygen deprivation group, the protein expression of E-cadherin was higher than that of glucose and oxygen deprivation group, and the protein expression of GRP78 and CHOP were lower than those of glucose and oxygen deprivation group (P < 0.05). The expression of TLR4 in Tasosartan+ PCDNA3.1-TLR4 group was higher than that in Tasosartan group, and the apoptosis rate was higher than that in Tasosartan group, the protein expression of α-SMA, Col Ⅰ, Fibronectin, GRP78, and CHOP was higher than those in Tasosartan group, while the protein expression of E-cadherin was lower than that in Tasosartan group (P < 0.05). Conclusion Tasosartan can reduce endoplasmic reticulum stress in HK-2 cells cultured with glucose and oxygen deprivation, thereby attenuating the cell damage induced by glucose and oxygen deprivation, and its effect is produced by inhibiting TLR4.
LIU Xiujuan1▲ WU Yu2 ZOU Xin1 YU Yanyan1 GENG Yanqiu3▲ SHUANG Feng4. Effect of Tasosartan on human renal tubular epithelial cells induced by glucose and oxygen deprivation and its mechanism[J]. 中国医药导报, 2021, 18(31): 7-11.
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