RRC ID 42751
著者 Yuki T, Ishihara S, Rumi MA, Ortega-Cava CF, Kadowaki Y, Kazumori H, Ishimura N, Amano Y, Moriyama N, Kinoshita Y.
タイトル Increased expression of midkine in the rat colon during healing of experimental colitis.
ジャーナル Am J Physiol Gastrointest Liver Physiol
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.
巻・号 291(4)
ページ G735-43
公開日 2006-10-1
DOI 10.1152/ajpgi.00388.2005
PII 291/4/G735
PMID 16959957
MeSH Animals Cell Line Chemokines, CXC / genetics Chemokines, CXC / metabolism Colitis / chemically induced Colitis / metabolism* Colitis / pathology Colon / metabolism* Cytokines / genetics Cytokines / metabolism* Dextran Sulfate / pharmacology Fibroblasts / metabolism Gene Expression Regulation* Interleukin-1 / metabolism Intestinal Mucosa / drug effects Intestinal Mucosa / metabolism Male Midkine Rats Rats, Sprague-Dawley Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism Wound Healing*
IF 3.725
引用数 16
WOS 分野 GASTROENTEROLOGY & HEPATOLOGY PHYSIOLOGY
リソース情報
ヒト・動物細胞 IEC 6(RCB0993)