The Role And Mechanism Of CLCC1 In Renal Tubular Cells Injury Induced By Oxygen-Glucose Deprivation/Reoxygenation

Background:Acute kidney injury(AKI)is an acute kidney disease caused by a variety of causes in a short period of time.Renal ischemia-reperfusion injury(IRI)is one of the main clinical causes of AKI,which can be caused by kidney transplantation,cardiac surgery,burns,and shock,etc.Studies have confirmed that endoplasmic reticulum stress(ERS)plays a significant role in the process of renal IRI,and inhibition of ERS may provide fresh ideas for the treatment of IRI-induced AKI.In recent years,some studies have reported that CLCC1,a chloride channel protein,is involved in the process of ERS and plays a crucial role in the disease.However,the role and mechanism of CLCC1 regulating ERS in renal IRI-induced AKI is still unclear.Objective:In this study,we investigate the role and underlying mechanism of CLCC1 regulating endoplasmic reticulum stress in IRI-induced AKI,to provide a novel therapeutic target for acute kidney injury.Methods:1.In vitro,renal tubular epithelial cells(BUMPT cells)were treated with tunicamycin(TM).After treatment,cells were collected to detect CLCC1 expression,endoplasmic reticulum stress and apoptosis.2.Clcc1 knockdown and CLCC1 overexpression cell lines were established and treated with tunicamycin.After incubation,cells were collected to detect endoplasmic reticulum stress and apoptosis.3.We employed a stable oxygen-glucose deprivation/reoxygenation(OGD/R)model in BUMPT cells to mimic the ishchemia reperfusion injury in vitro.Cells were collected at predetermined time points to detect CLCC1 expression,endoplasmic reticulum stress and apoptosis.4.Clcc1 knockdown and CLCC1 overexpression cell lines were established and treated with OGD/R.Collect cells at predetermined time points to detect endoplasmic reticulum stress and cell apoptosis.Results:1.Tunicamycin treatment induced a typical ERS and ERS-related apoptosis in BUMPT cells.2.The expression of Clcc1 mRNA was down-regulated in BUPMT cells after tunicamycin treatment.3.Clcc1 knockdown exacerbated tunicamycin-induced ERS and ERS associated apoptosis,Whereas CLCC1 overexpression alleviated these tunicamycin-induced changes.4.After OGD/R,BUMPT cells showed a remarkable ERS and ERS associated apoptosis in BUMPT cells.5.The expression of Clcc1 mRNA was down-regulated in BUPMT cells after OGD/R.6.Clcc1 knockdown promoted OGD/R-induced ERS and ERS-related apoptosis,Whereas CLCC1 overexpression alleviated these OGD/R-induced changes.Conclusion:CLCC1 attenuates OGD/R-induced acute tubular cell injury by inhibiting ERS-related apoptosis,and ultimately exerts a renoprotective effect.