| Project/Area Number |
17K17004
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatric surgery
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| Research Institution | Juntendo University |
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Principal Investigator |
Sueyoshi Ryo 順天堂大学, 医学部, 非常勤助教 (10724172)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 短腸症候群 / DPP4阻害薬 / タイト結合 / E-Cadeherin / Occludin / タイト結合蛋白 / E-Cadherin / バクテリアルトランスロケーション / 腸内細菌叢 / GLP-2 / 消化管 / 腸管免疫 / DPP４阻害薬 |
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| Outline of Final Research Achievements |
Purpose: Bacterial overgrowth commonly occurs and favors bacterial translocation in short bowel syndrome (SBS). Glucagon like peptide-2 (GLP-2) is effective for treating SBS but is rapidly inactivated by dipeptidyl peptidase IV (DPP4). DPP4 inhibitor (DPP4I) is known to be effective for treating SBS. Here, we investigated cell junction protein function following DPP4I administration in a mouse model of SBS. Methods: All control and DPP4I mice had 50% of their proximal small bowel resected. The functions of cell junction proteins were assessed by RT-PCR and immunohistochemistry. Results: E-Cadherin was significantly higher in the DPP4I group than in the control group. Positive staining for E-cadherin and occludin varied widely between the control and DPP4I groups. Conclusion: Up-regulation of E-cadherin and occludin by DPP4 inhibitor may be correlated with the anti-inflammatory action of DPP4 inhibitor. Therefore, DPP4 inhibitor may reduce bacterial translocation in SBS.
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| Academic Significance and Societal Importance of the Research Achievements |
短腸症候群に対して、海外で唯一認可されている薬剤がGLP-2アナログ製剤Teduglutideである。しかし、Teduglutideの欠点は2点ある（①皮下注射製剤である②投与中止すると薬効が減弱する）。DPP4阻害薬は経口摂取製剤であり、以前の研究にて投与中止後の薬効の持続性を証明しており、これらの欠点を補完し得る。
本研究ではE-CadeherinとOccludin に関してDPP4阻害薬による有意な変化を呈していた。この結果はDPP4阻害薬により、短腸症候群モデルマウスの腸管上皮細胞の腸管バリア機能の増強を示唆し、バクテリアルトランスロケーションの低減への可能性を示した。
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