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: Wataru Yoshioka, Tatsuya Kawaguchi, Nozomi Fujisawa, Keiko Aida-Yasuoka, Takao Shimizu, Fumio Matsumura, Chiharu Tohyama
• Journal: Scientific reports (Sci Rep) Vol. 4 Pg. 4042 (Feb 10 2014) ISSN: 2045-2322 [Electronic] England
• PMID: 24509627 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin-Like Growth Factor Binding Protein 1
• Polychlorinated Dibenzodioxins
• RNA, Messenger
• Receptors, Aryl Hydrocarbon
• Cytochrome P-450 CYP1A1
• Ptgs2 protein, mouse
• Cyclooxygenase 2
• Group IV Phospholipases A2
• Intramolecular Oxidoreductases
• PTGES protein, human
• Prostaglandin-E Synthases
• Ptges protein, mouse
• Dinoprostone

Topics

• Animals
• Cyclooxygenase 2 (biosynthesis)
• Cytochrome P-450 CYP1A1 (genetics)
• Dinoprostone (biosynthesis)
• Disease Models, Animal
• Female
• Gene Expression
• Group IV Phospholipases A2 (genetics, metabolism)
• Hydronephrosis (chemically induced, pathology)
• Insulin-Like Growth Factor Binding Protein 1 (genetics)
• Intramolecular Oxidoreductases (biosynthesis, genetics)
• Kidney (pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Polychlorinated Dibenzodioxins
• Prostaglandin-E Synthases
• RNA, Messenger (biosynthesis)
• Receptors, Aryl Hydrocarbon (genetics, metabolism)
• Signal Transduction (genetics)
• Up-Regulation