Tamoxifen downregulates connective tissue growth factor to ameliorate peritoneal fibrosis
Journal
Blood Purification
Journal Volume
31
Journal Issue
4
Pages
252-258
Date Issued
2011
Author(s)
Wu H.-Y.
Lien Y.-C.
Abstract
Peritoneal fibrosis (PF), including simple sclerosis and encapsulating peritoneal sclerosis (EPS), is a serious complication in patients on long-term peritoneal dialysis. Tamoxifen has successfully been used in treating EPS; however, the mechanism of tamoxifen in treating EPS fibrosis disorders remains unclear. This study demonstrates a possible antifibrotic mechanism of tamoxifen. A bleach-induced PF rat model was applied as the in vivo treatment target. Tamoxifen was intraperitoneally injected daily to treat PF. The PF scores and thickness of the submesothelial zone over the liver surface were measured as indicators for the severity of PF. Human peritoneal mesothelial cells (HPMC) were used as an in vitro model to test the antifibrotic effect of tamoxifen. Gene expressions of transforming growth factors-β (TGF-β), connective tissue growth factor (CTGF) and collagen were investigated using quantitative polymerase chain reactions. In HPMC, tamoxifen showed paradoxical effects between collagen I and TGF-β. Tamoxifen also inhibited TGF-β-induced collagen and CTGF. The possible antifibrotic effect of tamoxifen is through inhibiting CTGF to block collagen synthesis, although it enhances TGF-β which increases fibrosis. These results provide a possible molecular mechanism for tamoxifen. Copyright ? 2011 S. Karger AG.
SDGs
Other Subjects
collagen type 1; connective tissue growth factor; tamoxifen; transforming growth factor beta; animal experiment; animal model; animal tissue; article; controlled study; disease severity; down regulation; gene expression; histopathology; human; human cell; in vitro study; in vivo study; male; mesothelium; mesothelium cell; nonhuman; peritoneal fibrosis; peritoneum cell; polymerase chain reaction; priority journal; protein synthesis inhibition; quantitative analysis; rat; thickness; Animals; Antineoplastic Agents, Hormonal; Cells, Cultured; Collagen Type I; Connective Tissue Growth Factor; Down-Regulation; Extracellular Matrix; Gene Expression Regulation; Humans; Male; Peritoneal Fibrosis; Rats; Rats, Wistar; Sodium Hypochlorite; Tamoxifen; Transforming Growth Factor beta
Type
journal article