The mechanism of increased smad7 expression in the intestinal mucosa of inflammatory bowel disease and the exploitation of a new therapy

• Project/Area Number: 25460952
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyushu University
• Principal Investigator: Nakamura Kazuhiko 九州大学, 大学病院, 助教 (00274449)
• Co-Investigator(Kenkyū-buntansha): IHARA Eikichi 九州大学, 大学病院, 助教 (80612390)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 炎症性腸疾患 / smad7 / 炎症性サイトカイン / TGF-β / TGF-beta / proinflammatory cytokine / サイトカイン / シグナル伝達

Outline of Final Research Achievements

Mouse CD4+ T cells were stimulated with the addition of various cytokines. The expression level of smad7 protein was analyzed by western blot analysis. Smad7 expression was decreased by IL-1β, IFN-γ and TNF-α and increased by TGF-β. Smad7 mRNA expression was analyzed by quantitative PCR using biopsy samples under gastrointestinal endoscopy. Smad7 expression was decreased in active phase of refractory ulcerative colitis patients.
Proinflammatory cytokines such as IL-1β, IFN-γ and TNF-α were considered to be inhibitors and TGF-β was considered to be a promoter of smad7 expression. In the refractory ulcerative colitis patients, smad7 expression might be downregulated by increased proinflammatory cytokines.