title: Predominant role of cytosolic phospholipase A2α in dioxin-induced neonatal hydronephrosis in mice.
abstract: Hydronephrosis is a common disease characterized by dilation of the renal pelvis and calices, resulting in loss of kidney function in the most severe cases. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces nonobstructive hydronephrosis in mouse neonates through upregulation of prostaglandin E2 (PGE2) synthesis pathway consisting of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) by a yet unknown mechanism. We here studied possible involvement of cytosolic phospholipase A2α (cPLA2α) in this mechanism. To this end, we used a cPLA2α-null mouse model and found that cPLA2α has a significant role in the upregulation of the PGE2 synthesis pathway through a noncanonical pathway of aryl hydrocarbon receptor. This study is the first to demonstrate the predominant role of cPLA2α in hydronephrosis. Elucidation of the pathway leading to the onset of hydronephrosis using the TCDD-exposed mouse model will deepen our understanding of the molecular basis of nonobstructive hydronephrosis in humans.
authors: 1] Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan [2] Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
authors: Wataru
authors: W
authors: Yoshioka
authors: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors: Tatsuya
authors: T
authors: Kawaguchi
authors: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors: Nozomi
authors: N
authors: Fujisawa
authors: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors: Keiko
authors: K
authors: Aida-Yasuoka
authors: Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors: Takao
authors: T
authors: Shimizu
authors: Department of Environmental Toxicology and Center for Environmental Health Sciences, University of California, Davis, CA 95616, USA.
authors: Fumio
authors: F
authors: Matsumura
authors: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors: Chiharu
authors: C
authors: Tohyama
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D054513:Group IV Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D006869:Hydronephrosis / Q000139:chemically induced / Q000473:pathology*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D007668:Kidney / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072317:Polychlorinated Dibenzodioxins; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000096:biosynthesis; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D054513:Group IV Phospholipases A2; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone