title: mPGES-1-derived PGE2 contributes to adriamycin-induced podocyte injury.
abstract: Podocyte damage is a common pathological feature in many types of glomerular diseases and is involved in the occurrence and progression of kidney disease. However, the pathogenic mechanisms leading to podocyte injury are still uncertain. The present study was undertaken to investigate the role of microsomal PGE synthase (mPGES)-1 in adriamycin (ADR)-induced podocyte injury as well as the underlying mechanism. In both mouse kidneys and in vitro podocytes, application of ADR remarkably enhanced mPGES-1 expression in line with a stimulation of cyclooxygenase-2. Interestingly, inhibition of mPGES-1 with a small interfering RNA approach significantly attenuated ADR-induced downregualtion of podocin and nephrin. Moreover, ADR-induced podocyte apoptosis was also markedly blocked in parallel with blunted caspase-3 induction. In agreement with the improvement of cell phenotypic alteration and apoptosis, the enhanced inflammatory markers of IL-1β and TNF-α were also significantly suppressed by mPGES-1 silencing. More importantly, in mPGES-1-deficient mice, albuminuria induced by ADR showed a remarkable attenuation in line with decreased urinary output of PGE2 and TNF-α, highly suggesting an in vivo role of mPGES-1 in mediating podocyte injury. In summary, findings from the present study offered the first evidence demonstrating a pathogenic role of mPGES-1 in mediating ADR-induced podocyte injury possibly via triggering an inflammatory response.
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Affiliated with Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; and Nanjing Key Laboratory of Pediatrics, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Affiliated with Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; and Nanjing Key Laboratory of Pediatrics, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Affiliated with Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; and Nanjing Key Laboratory of Pediatrics, Nanjing, China.
authors.forename: Yimei
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Affiliated with Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; and Nanjing Key Laboratory of Pediatrics, Nanjing, China.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Affiliated with Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; and Nanjing Key Laboratory of Pediatrics, Nanjing, China.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Affiliated with Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; and Nanjing Key Laboratory of Pediatrics, Nanjing, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Affiliated with Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; and Nanjing Key Laboratory of Pediatrics, Nanjing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Affiliated with Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; and Nanjing Key Laboratory of Pediatrics, Nanjing, China.
authors.forename: Guangrui
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Affiliated with Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; and Nanjing Key Laboratory of Pediatrics, Nanjing, China.
authors.forename: Songming
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Affiliated with Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; and Nanjing Key Laboratory of Pediatrics, Nanjing, China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Affiliated with Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; and Nanjing Key Laboratory of Pediatrics, Nanjing, China zhaihua@njmu.edu.cn.
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D004317:Doxorubicin / Q000633:toxicity*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D007674:Kidney Diseases / Q000201:enzymology / Q000209:etiology*; D008297:Male; D008807:Mice, Inbred BALB C; D050199:Podocytes / Q000187:drug effects / Q000201:enzymology*; D000071876:Prostaglandin-E Synthases
chemical_list: D004317:Doxorubicin; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone
keywords: apoptosis; microsomal prostaglandin E synthase-1; podocyte; prostaglandin E2