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Deletion of connective tissue growth factor ameliorates peritoneal fibrosis by inhibiting angiogenesis and inflammation.
- Source :
-
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 2018 Jun 01; Vol. 33 (6), pp. 943-953. - Publication Year :
- 2018
-
Abstract
- Background: Connective tissue growth factor (CTGF/CCN2) regulates the signalling of other growth factors and promotes fibrosis. CTGF is increased in mice and humans with peritoneal fibrosis. Inhibition of CTGF has not been examined as a potential therapeutic target for peritoneal fibrosis because systemic CTGF knockout mice die at the perinatal stage.<br />Methods: To study the role of CTGF in peritoneal fibrosis of adult mice, we generated CTGF conditional knockout (cKO) mice by crossing CTGF floxed mice with RosaCreERT2 mice. We administered tamoxifen to Rosa-CTGF cKO mice to delete the CTGF gene throughout the body. We induced peritoneal fibrosis by intraperitoneal injection of chlorhexidine gluconate (CG) in wild-type and Rosa-CTGF cKO mice.<br />Results: Induction of peritoneal fibrosis in wild-type mice increased CTGF expression and produced severe thickening of the peritoneum. In contrast, CG-treated Rosa-CTGF cKO mice exhibited reduced thickening of the peritoneum. Peritoneal equilibration test revealed that the excessive peritoneal small-solute transport in CG-treated wild-type mice was normalized by CTGF deletion. CG-treated Rosa-CTGF cKO mice exhibited a reduced number of αSMA-, Ki67-, CD31- and MAC-2-positive cells in the peritoneum. Analyses of peritoneal mRNA showed that CG-treated Rosa-CTGF cKO mice exhibited reduced expression of Cd68, Acta2 (αSMA), Pecam1 (CD31) and Vegfa.<br />Conclusions: These results indicate that a deficiency of CTGF can reduce peritoneal thickening and help to maintain peritoneal function by reducing angiogenesis and inflammation in peritoneal fibrosis. These results suggest that CTGF plays an important role in the progression of peritoneal fibrosis.
- Subjects :
- Angiogenesis Inhibitors pharmacology
Animals
Connective Tissue Growth Factor physiology
Humans
Inflammation etiology
Inflammation metabolism
Inflammation pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Neovascularization, Pathologic etiology
Neovascularization, Pathologic metabolism
Neovascularization, Pathologic pathology
Peritoneal Fibrosis etiology
Peritoneal Fibrosis metabolism
Peritoneal Fibrosis pathology
Signal Transduction drug effects
Connective Tissue Growth Factor antagonists & inhibitors
Inflammation prevention & control
Neovascularization, Pathologic prevention & control
Peritoneal Fibrosis prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2385
- Volume :
- 33
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
- Publication Type :
- Academic Journal
- Accession number :
- 29165602
- Full Text :
- https://doi.org/10.1093/ndt/gfx317