title: Inhibition of COX-2/PGE2 cascade ameliorates cisplatin-induced mesangial cell apoptosis.
abstract: Cisplatin is one of the most potent cytotoxic drug for the treatment of many types of cancer. However, the side effects on normal tissues, particularly on the kidney, greatly limited its use in clinic. Emerging evidence demonstrated that cisplatin could directly cause mesangial cell apoptosis, while the potential mechanism is still elusive. Here we examined the contribution of COX-2 in cisplatin-induced mesangial cell apoptosis. Firstly, we found cisplatin induced cell apoptosis in mesangial cells shown by increased number of apoptotic cells in parallel with the upregulation of Bax and the downregulation of Bcl-2. Interestingly, cisplatin-induced cell apoptosis was accompanied by an upregulation of COX-2 at both mRNA and protein levels in dose- and time-dependent manners. Importantly, inhibition of COX-2 via a specific COX-2 inhibitor celecoxib markedly blocked cisplatin-induced mesangial cell apoptosis as evidenced by the decreased number of apoptotic cells, blocked increments of cleaved caspase-3 and Bax, and reversed Bcl-2 downregulation. Meanwhile, cisplatin-induced PGE2 production was markedly blocked by the treatment of celecoxib. In conclusion, this study indicated that COX-2/PGE2 cascade activation mediated cisplatin-induced mesangial cell apoptosis. The findings not only offered new insights into the understanding of cisplatin nephrotoxicity but also provided the therapeutic potential by targeting COX-2/PGE2 cascade in treating cisplatin-induced kidney injury.
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical UniversityNanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical UniversityNanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China.
authors.forename: Yunwen
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical University Nanjing 210008, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University Nanjing 210008, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical UniversityNanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical UniversityNanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical UniversityNanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical UniversityNanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical UniversityNanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical UniversityNanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China.
authors.forename: Guixia
authors.initials: G
authors.lastname: Ding
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical UniversityNanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China.
authors.forename: Songming
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical UniversityNanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Nephrology, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical UniversityNanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical UniversityNanjing 210008, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
keywords: COX-2; Cisplatin; PGE2; apoptosis; mesangial cell