title: Relaxin attenuates aristolochic acid induced human tubular epithelial cell apoptosis in vitro by activation of the PI3K/Akt signaling pathway.
abstract: Aristolochic acid nephropathy remains a leading cause of chronic kidney disease (CKD), however few treatment strategies exist. Emerging evidence has shown that H2 relaxin (RLX) possesses powerful antifibrosis and anti-apoptotic properties, therefore we aimed to investigate whether H2 relaxin can be employed to reduce AA-induced cell apoptosis. Human proximal tubular epithelial (HK-2) cells exposed to AA-I were treated with or without administration of H2 RLX. Cell viability was examined using the WST-8 assay. Apoptotic morphologic alterations were observed using the Hoechst 33342 staining method. Apoptosis was detected using flow cytometry. The expression of caspase 3, caspase 8, caspase 9, ERK1/2, Bax, Bcl-2, and Akt proteins was determined by Western blot. Co-treatment with RLX reversed the increased apoptosis observed in the AA-I only treated group. RLX restored expression of phosphorylated Akt which found to be decreased in the AA-I only treated cells. RLX co-treatment led to a decrease in the Bax/Bcl-2 ratio as well as the cleaved form of caspase-3 compared to the AA-I only treated cells. This anti-apoptotic effect of RLX was attenuated by co-administration of the Akt inhibitor LY294002. The present study demonstrated H2 RLX can decrease AA-I induced apoptosis through activation of the PI3K/Akt signaling pathway.
authors.affiliation: Department of Nephrology, Hangzhou First People's Hospital, Nanjing Medical University, No. 261, Huansha Road, Hangzhou, 310006, Zhejiang, China.
authors.forename: Xiang-Cheng
authors.initials: XC
authors.lastname: Xie
authors.affiliation: Department of Nephrology, Hangzhou First People's Hospital, Nanjing Medical University, No. 261, Huansha Road, Hangzhou, 310006, Zhejiang, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, Hangzhou First People's Hospital, Nanjing Medical University, No. 261, Huansha Road, Hangzhou, 310006, Zhejiang, China.
authors.forename: Qun-Hong
authors.initials: QH
authors.lastname: Xu
authors.affiliation: Department of Nephrology, Hangzhou First People's Hospital, Nanjing Medical University, No. 261, Huansha Road, Hangzhou, 310006, Zhejiang, China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Nephrology, Jiangyin People's Hospital, No. 163, Shoushan Road, Jiangyin, 214400, Jiangsu, China.
authors.forename: Wen-Kai
authors.initials: WK
authors.lastname: Xia
authors.affiliation: Department of Nephrology, Hangzhou First People's Hospital, Nanjing Medical University, No. 261, Huansha Road, Hangzhou, 310006, Zhejiang, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Hangzhou First People's Hospital, Nanjing Medical University, No. 261, Huansha Road, Hangzhou, 310006, Zhejiang, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Hangzhou First People's Hospital, Nanjing Medical University, No. 261, Huansha Road, Hangzhou, 310006, Zhejiang, China. feixiaoabc@yeah.net.
authors.forename: Xiao
authors.initials: X
authors.lastname: Fei
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D034341:Aristolochic Acids / Q000633:toxicity*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012065:Relaxin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D034341:Aristolochic Acids; D051028:bcl-2-Associated X Protein; D012065:Relaxin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases
keywords: Apoptosis; Aristolochic acid nephropathy; Human relaxin; Kidney fibrosis