HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Microsomal prostaglandin E synthase 1 deletion retards renal disease progression but exacerbates anemia in mice with renal mass reduction.

Abstract
Microsomal prostaglandin E synthase 1 (mPGES-1) is a cytokine-inducible enzyme responsible for generation of prostaglandin E(2) (PGE(2)) during the inflammatory response. In the present study, we investigated the role of mPGES-1 in the development of chronic renal failure in mice with 5/6 nephrectomy (Nx). After 4 weeks of Nx, wild-type mice with renal mass reduction exhibited increased blood urea nitrogen, plasma creatinine and phosphorus concentrations, and defective urine concentrating capability, all of which were significantly attenuated by mPGES-1 deletion. The Nx wild-type mice developed a 2.6-fold increase in urinary albumin excretion, accompanied by glomerulosclerosis and reduction of nephrin and wild-type 1 expression in the remnant kidney. In contrast, the Nx KO mice had normal albuminuria with improvement of glomerular injury. Nx-induced increases in circulating and renal tumor necrosis factor 1α and renal interleukin 1β and monocyte chemoattractant protein 1 expressions were all remarkably attenuated or abolished by mPGES-1 deletion. Paradoxically, the Nx knockout mice developed worsened anemia, accompanied by impaired erythropoietin synthesis. The coinduction of mPGES-1 and cyclooxygenase 2 but not cyclooxygenase 1 mRNA expressions, along with increased PGE(2) synthesis, was demonstrated in the remnant kidney of wild-type mice. mPGES-1 deletion remarkably reduced renal PGE(2) content and urinary PGE(2) excretion after renal ablation but had a limited effect on the baseline PGE(2) production. We conclude that mPGES-1 deletion ameliorates chronic renal failure in the mouse model of renal mass reduction, and mPGES-1 deletion paradoxically exacerbates anemia in this model likely via suppression of erythropoietin synthesis.
AuthorsZhanjun Jia, Haiping Wang, Tianxin Yang
JournalHypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 59 Issue 1 Pg. 122-8 (Jan 2012) ISSN: 1524-4563 [Electronic] United States
PMID22106404 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases
  • Ptges protein, mouse
Topics
  • Anemia (metabolism, physiopathology)
  • Animals
  • Blood Pressure (physiology)
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gene Deletion
  • Intramolecular Oxidoreductases (genetics, metabolism)
  • Kidney Concentrating Ability (physiology)
  • Kidney Glomerulus (metabolism, pathology)
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout
  • Microsomes (enzymology)
  • Nephrectomy
  • Prostaglandin-E Synthases
  • Renal Insufficiency, Chronic (metabolism, pathology, physiopathology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: