Back to Search
Start Over
The intrinsic prostaglandin E2-EP4 system of the renal tubular epithelium limits the development of tubulointerstitial fibrosis in mice.
- Source :
-
Kidney International . Jul2012, Vol. 82 Issue 2, p158-171. 14p. 4 Color Photographs, 7 Graphs. - Publication Year :
- 2012
-
Abstract
- Inflammatory responses in the kidney lead to tubulointerstitial fibrosis, a common feature of chronic kidney diseases. Here we examined the role of prostaglandin E2 (PGE2) in the development of tubulointerstitial fibrosis. In the kidneys of wild-type mice, unilateral ureteral obstruction leads to progressive tubulointerstitial fibrosis with macrophage infiltration and myofibroblast proliferation. This was accompanied by an upregulation of COX-2 and PGE2 receptor subtype EP4 mRNAs. In the kidneys of EP4 gene knockout mice, however, obstruction-induced histological alterations were significantly augmented. In contrast, an EP4-specific agonist significantly attenuated these alterations in the kidneys of wild-type mice. The mRNAs for macrophage chemokines and profibrotic growth factors were upregulated in the kidneys of wild-type mice after ureteral obstruction. This was significantly augmented in the kidneys of EP4-knockout mice and suppressed by the EP4 agonist but only in the kidneys of wild-type mice. Notably, COX-2 and MCP-1 proteins, as well as EP4 mRNA, were localized in renal tubular epithelial cells after ureteral obstruction. In cultured renal fibroblasts, another EP4-specific agonist significantly inhibited PDGF-induced proliferation and profibrotic connective tissue growth factor production. Hence, an endogenous PGE2-EP4 system in the tubular epithelium limits the development of tubulointerstitial fibrosis by suppressing inflammatory responses. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00852538
- Volume :
- 82
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Kidney International
- Publication Type :
- Academic Journal
- Accession number :
- 77406569
- Full Text :
- https://doi.org/10.1038/ki.2012.115