期刊
PERITONEAL DIALYSIS INTERNATIONAL
卷 42, 期 5, 页码 522-529出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/08968608211051572
关键词
alpha-SMA; epimorphin; PDGFR-beta; peritoneal fibrosis; TGF-beta
资金
- JSPS KAKENHI [17K09739]
- Grants-in-Aid for Scientific Research [17K09739] Funding Source: KAKEN
The study found that epimorphin can suppress the expression of fibrosis-associated markers in a peritoneal fibrosis mouse model and cultured cells.
Background: Long-term peritoneal dialysis results in functional and histopathological alterations of the peritoneal membrane, leading to peritoneal fibrosis (PF). The mechanism of PF has not been fully elucidated, and at present there is no effective therapy for PF. Epimorphin is a mesenchymal protein that not only regulates morphogenesis in organ development but is implicated in tissue repair. However, the role of epimorphin in PF has not yet been clarified. Methods: PF was induced in C57/Bl6 mice by intraperitoneal injection of chlorhexidine gluconate (CG-injected mice) three times a week for 3 weeks. The parietal peritoneum was subsequently dissected and assessed by Masson's trichrome staining, and epimorphin expression was analysed by immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR). Furthermore, epimorphin-positive regions were analysed by multiple immunofluorescence staining using fibrosis-associated markers. In addition, normal rat fibroblast cells (NRK-49F) were treated with transforming growth factor-beta (TGF-beta) in the presence or absence of epimorphin. The expression of fibrosis-associated markers was assessed by real-time RT-PCR. Results: In CG-injected mice, Masson's trichrome staining showed marked thickening of the submesothelial compact zone. Weak epimorphin expression was observed in the narrow submesothelial compact zone beneath the mesothelial cells in control mice; however, epimorphin expression was stronger in the submesothelial compact zone in CG-injected mice. Epimorphin expression was observed mainly in alpha-smooth muscle actin (alpha-SMA)-positive myofibroblasts. Epimorphin suppressed the TGF-beta-induced upregulation of alpha-SMA and platelet-derived growth factor receptor-beta in cultured cells. Conclusions: Our results suggest that epimorphin may be a therapeutic target for fibrotic diseases of the peritoneum.
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