Predominant Role of Cytosolic Phospholipase A2α in Dioxin-induced Neonatal Hydronephrosis in Mice

• Published in: Scientific reports 2014-02, Vol.4 (1), p.4042, Article 4042
• Main Authors: Yoshioka, Wataru, Kawaguchi, Tatsuya, Fujisawa, Nozomi, Aida-Yasuoka, Keiko, Shimizu, Takao, Matsumura, Fumio, Tohyama, Chiharu
• Format: Article
• Language: English
• Subjects: 38/88; 631/136/1425; 631/80/304; 64/110; 692/699/1585/2762; 692/699/1585/2763; Animals; Cyclooxygenase 2 - biosynthesis; Cytochrome P-450 CYP1A1 - genetics; Dinoprostone - biosynthesis; Disease Models, Animal; Female; Gene Expression; Group IV Phospholipases A2 - genetics; Group IV Phospholipases A2 - metabolism; Humanities and Social Sciences; Hydronephrosis - chemically induced; Hydronephrosis - pathology; Insulin-Like Growth Factor Binding Protein 1 - genetics; Intramolecular Oxidoreductases - biosynthesis; Intramolecular Oxidoreductases - genetics; Kidney - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Polychlorinated Dibenzodioxins; Prostaglandin-E Synthases; Receptors, Aryl Hydrocarbon - genetics; Receptors, Aryl Hydrocarbon - metabolism; RNA, Messenger - biosynthesis; Science; Signal Transduction - genetics; Up-Regulation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep04042

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 E 2 (PGE 2 ) 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 A 2 α (cPLA 2 α) in this mechanism. To this end, we used a cPLA 2 α-null mouse model and found that cPLA 2 α has a significant role in the upregulation of the PGE 2 synthesis pathway through a noncanonical pathway of aryl hydrocarbon receptor. This study is the first to demonstrate the predominant role of cPLA 2 α 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.