期刊
CURRENT MEDICAL SCIENCE
卷 42, 期 2, 页码 341-347出版社
SPRINGER
DOI: 10.1007/s11596-022-2513-8
关键词
thrombospondin 1; HK-2 cells; endoplasmic reticulum stress; apoptosis
This study investigated the role and mechanism of thrombospondin 1 (TSP1) in regulating endoplasmic reticulum stress and apoptosis in human renal tubular epithelial cells (HK-2 cells). The results showed that overexpression of TSP1 activated endoplasmic reticulum stress through the ATF6-CHOP axis, inhibited cell proliferation, and promoted apoptosis and endoplasmic reticulum stress in HK-2 cells.
Objective The goal of this study is to investigate the role and mechanism of endoplasmic reticulum stress and apoptosis regulated by thrombospondin 1 (TSP1) in human renal tubular epithelial cells (HK-2 cells). Methods HK-2 cells were exposed to high concentrations of glucose (HG). The endoplasmic reticulum stress inhibitor 4-phenylbutyric acid (4-PBA) was administered by transfecting TSP1 or an empty vector to explore the mechanism of the endoplasmic reticulum response regulated by TSP1 and stress in renal cell apoptosis. The effects of TSP1 and 4-PBA on the proliferation and apoptosis of HK-2 cells under HG conditions were assessed using Cell counting kit-8 and flow cytometry. Western blotting was used to detect the apoptosis- and endoplasmic reticulum stress-related protein expression regulated by TSP1 and 4-PBA. Results HG treatment induced high cell apoptosis, abundantly expressed TSP1 level and restrained viability in HK-2 cells. Overexpression of TSP1 significantly inhibited the proliferation of and facilitated apoptosis of HK-2 cells under HG conditions. Administration of endoplasmic reticulum stress inhibitor 4-PBA after overexpression of TSP1 antagonized the inhibitory proliferation and promoted apoptosis rate in HG-triggered HK-2 cells induced by TSP1 overexpression. 4-PBA treatment significantly hindered the expression of endoplasmic reticulum stress markers, such as PERK, ATF4, ATF6, p-eIF2 alpha, IRE1, CHOP and XBP1, suggesting that the administration of 4-PBA was successful. Conclusion Overexpression of TSP1 activated endoplasmic reticulum stress by regulating the ATF6-CHOP axis. TSP1 restrained cell proliferation, and promoted apoptosis and endoplasmic reticulum stress by activating the ATF6-CHOP axis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据