title: Deficiency of mPGES-1 exacerbates renal fibrosis and inflammation in mice with unilateral ureteral obstruction.
abstract: Microsomal prostaglandin E2synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2to prostaglandin E2(PGE2), plays an important role in a variety of inflammatory diseases. We investigated the contribution of mPGES-1 to renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) for 7 days using wild-type (WT) and mPGES-1 knockout (KO) mice. UUO induced increased mRNA and protein expression of mPGES-1 and cyclooxygenase-2 in WT mice. UUO was associated with increased renal PGE2content and upregulated PGE2receptor (EP) 4 expression in obstructed kidneys of both WT and mPGES-1 KO mice; EP4 expression levels were higher in KO mice with UUO than those in WT mice. Protein expression of NLRP3 inflammasome components ASC and interleukin-1β was significantly increased in obstructed kidneys of KO mice compared with that in WT mice. mRNA expression levels of fibronectin, collagen III, and transforming growth factor-β1 (TGF-β1) were significantly higher in obstructed kidneys of KO mice than that in WT mice. In KO mice, protein expression of fibronectin and collagen III was markedly increased in obstructed kidneys compared with WT mice, which was associated with increased phosphorylation of protein kinase B (AKT). EP4 agonist CAY10598 attenuated increased expression of collagen I and fibronectin induced by TGF-β1 in inner medullary collecting duct 3 cells. Moreover, CAY10598 prevented the activation of NLRP3 inflammasomes induced by angiotensin II in human proximal tubule cells (HK2). In conclusion, these findings suggested that mPGES-1 exerts a potentially protective effect against renal fibrosis and inflammation induced by UUO in mice.
authors: Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors: Renfei
authors: R
authors: Luo
authors: Department of Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and.
authors: Yutaka
authors: Y
authors: Kakizoe
authors: Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors: Feifei
authors: F
authors: Wang
authors: Neurosurgery Department, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
authors: Xiang
authors: X
authors: Fan
authors: Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors: Shan
authors: S
authors: Hu
authors: Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Department of Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; and.
authors: Tianxin
authors: T
authors: Yang
authors: Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors: Weidong
authors: W
authors: Wang
authors: Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; lichl3@mail.sysu.edu.cn.
authors: Chunling
authors: C
authors: Li
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism; D058847:Inflammasomes / Q000187:drug effects / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism; D008822:Mice, Transgenic; D000071876:Prostaglandin-E Synthases / Q000172:deficiency* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology
chemical_list: C000598602:CAY10598; D005353:Fibronectins; D058847:Inflammasomes; D011760:Pyrrolidinones; D013777:Tetrazoles; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone
keywords: AKT; fibrosis; inflammasomes; prostaglandin