| Project/Area Number |
15K08313
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Uchiyama Kazuhiko 京都府立医科大学, 医学(系)研究科(研究院), 助教 (50298428)
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| Co-Investigator(Kenkyū-buntansha) |
内藤 裕二 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (00305575)
高木 智久 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (70405257)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 大腸上皮細胞 / 筋繊維芽細胞 / 短鎖脂肪酸 / 粘膜再生 / Wnt5a / IBD / 創傷治癒 / mucosal healing / butyrate / Hsp25 / YAMC細胞 / DSS腸炎 |
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| Outline of Final Research Achievements |
In this study, two key factors were identifed that have important and counterbalancing roles regulating intestinal epithelial growth processes: pericrypt myofbroblast-derived Wnt5a and the microbial metabolite butyrate.
Intracellular Hsp25 inhibited YAMC proliferation and YAMC cell proliferation were enhanced via reduction of Hsp25 under butyrate condition with myofibroblasts conditioned medium and MS analysis revealed that the factor in conditioned medium was Wnt5a, especially a part of full length of Wnt5a: Wnt5a peptide (36mer amino acid). Synthesized Wnt5a peptide also reduced butyrate induced Hsp25 and promoted proliferation via β-catenin nuclear translocation in YAMC. Wnt5a peptide treatment in DSS colitis recovery phase model showed the quick recover compared to control.
We conclude that Wnt5a peptide has an activity to promote colonic epithelial proliferation via reduction of Hsp25 under butyrate condition.
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