Increased expression of epimorphin in a peritoneal fibrosis mouse model
| Autor: | Tomohiro Tomiyasu, Muneharu Yamada, Dan Inoue, Shuhei Komatsu, Noriko Yoshikawa, Tadasu Kojima, Yohei Hirai, Takashi Oda, Takahiro Uchida |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pathology
medicine.medical_specialty Membrane Glycoproteins business.industry medicine.medical_treatment Peritoneal membrane Peritoneal Fibrosis General Medicine Fibrosis Peritoneal dialysis Cell Line Rats Disease Models Animal Mice Nephrology Transforming Growth Factor beta medicine Animals Peritoneum business Peritoneal Dialysis |
| Zdroj: | Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 42(5) |
| ISSN: | 1718-4304 |
| Popis: | 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-β (TGF-β) 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 α-smooth muscle actin (α-SMA)-positive myofibroblasts. Epimorphin suppressed the TGF-β-induced upregulation of α-SMA and platelet-derived growth factor receptor-β in cultured cells. Conclusions: Our results suggest that epimorphin may be a therapeutic target for fibrotic diseases of the peritoneum. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|