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Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
Increased expression of midkine in the rat colon during healing of experimental colitis
Takafumi Yuki1, Shunji Ishihara, M A K Rumi
1Dept. of Gastroenterology and Hepatology, Shimane Medical Univ. School of Medicine, 89-1, Enya-cho, Izumo, Shimane 693-0021, Japan.
Abstract:
Midkine (MK) is a unique growth and differentiation factor that modulates the proliferation and migration of various cells; however, little is known regarding its relationship to intestinal diseases. The aim of this study was to investigate MK expression and its role in dextran sulfate sodium (DSS)-induced colitis in rats. The expressions of MK, receptor-like protein-tyrosine phosphatase (RPTP)-beta, and proinflammatory cytokines were examined in rat colonic tissues after the development of DSS-induced colitis using Northern blotting, immunohistochemistry, and laser-capture microdissection (LCM) coupled with RT-PCR. The effects of MK on the migration of intestinal epithelial cells (IEC-6) were also evaluated in vitro using an intestinal wound repair model. MK expression was significantly increased in damaged colonic mucosa, mainly from day 3 to day 5 after the end of DSS administration, with abundant MK immunoreactive signals detected in submucosal fibroblasts. Expressions of proinflammatory cytokines were most strongly induced on day 1, which preceded the augmentation of MK expression. Results of LCM coupled with RT-PCR clearly indicated RPTP-beta expression in colonic epithelial cells. The migration assay showed that wound repair in the MK-treated groups was accelerated dose dependently. The present results showed for the first time that intestinal inflammation upregulates the MK-RPTP-beta system, which may stimulate mucosal regeneration during the process of healing of colitis. Additional investigations regarding the role of MK may contribute to the development of new options for the treatment of inflammatory bowel diseases.
Insights
Midkine (MK) expression increases in rat colitis, promoting intestinal epithelial cell migration and wound repair. This suggests MK and RPTP-beta may aid mucosal regeneration in inflammatory bowel diseases.
Area of Science:
- Gastroenterology
- Cell Biology
- Molecular Biology
Background:
- Midkine (MK) is a growth factor influencing cell proliferation and migration.
- Its role in intestinal diseases, particularly colitis, remains largely unexplored.
- Understanding MK's function is crucial for developing new treatments for inflammatory bowel diseases.
Purpose of the Study:
- To investigate Midkine (MK) expression and its role in dextran sulfate sodium (DSS)-induced colitis in rats.
- To examine the relationship between MK, RPTP-beta, and proinflammatory cytokines in colitis.
- To evaluate the effect of MK on intestinal epithelial cell migration in vitro.
Main Methods:
- Northern blotting, immunohistochemistry, and laser-capture microdissection (LCM) coupled with RT-PCR were used to analyze rat colonic tissues.
- DSS-induced colitis model in rats was established to study disease progression.
- In vitro intestinal wound repair model using intestinal epithelial cells (IEC-6) assessed MK's effect on migration.
Main Results:
- MK expression significantly increased in damaged colonic mucosa during colitis, particularly from day 3 to day 5 post-DSS administration.
- MK immunoreactive signals were predominantly found in submucosal fibroblasts.
- Proinflammatory cytokine expression peaked on day 1, preceding the rise in MK levels.
- RPTP-beta expression was confirmed in colonic epithelial cells via LCM and RT-PCR.
- MK treatment accelerated intestinal epithelial cell migration and wound repair in a dose-dependent manner.
Conclusions:
- Intestinal inflammation upregulates the Midkine (MK)-RPTP-beta system.
- This system may play a significant role in stimulating mucosal regeneration during colitis healing.
- Further research into MK's function could lead to novel therapeutic strategies for inflammatory bowel diseases.
