Therapeutic strategies for intractable respiratory diseases through mesenchymal stem cells derived from pulmonary vascular endothelial cells
| Project/Area Number |
17H04181
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
西村 倫太郎 千葉大学, 大学院医学研究院, 特任助教 (00756091)
坂尾 誠一郎 千葉大学, 大学院医学研究院, 准教授 (80431740)
鈴木 敏夫 千葉大学, 大学院医学研究院, 特任助教 (70771856)
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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 |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | 肺血管内皮細胞 / ARDS / CD26 / DPP4 / LPS / 内皮間葉転換 / 肺動脈性肺高血圧症 / GFPマウス / complete EndMT / partial EndMT / 間葉系細胞 / 分子細胞呼吸器学 / 間葉系幹細胞 / LPS肺障害 / DPP4阻害薬 / 肺微小血管内皮細胞 / 肺血管障害 / 肺線維症 / 肺高血圧症 / COPD |
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| Outline of Final Research Achievements |
Pulmonary vascular endothelial cells (PVECs) function as an important pro-inflammatory source in ARDS, suggesting that modulation of inflammatory events at the endothelial level may have a therapeutic benefit. Dipeptidyl peptidase-4 (DPP4) inhibitors have been reported to have possible anti-inflammatory effects. However, the potential antiinflammatory effects of DPP4 inhibition on PVEC function and ARDS pathophysiology are unknown. Therefore, we evaluated the effects of sitagliptin, a DPP4 inhibitor in wide clinical use, on LPS-induced lung injury in mice and in human lung ECs in vitro. In summary, sitagliptin attenuates LPS-induced lung injury in mice and exerts anti-inflammatory effects on HLMVECs. These novel observations indicate DPP4 inhibitors may have potential as therapeutic drugs for ARDS.
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| Academic Significance and Societal Importance of the Research Achievements |
難治性呼吸器疾患に対する新規治療戦略の開拓のターゲットとして、ARDSにおける肺血管内皮細胞の役割に注目している。ARDSに対する有効な治療方法は確立しておらず、何らかの新規治療戦略が必要である。ARDS初期の過剰な炎症反応を抑制しうる一つの分子が多くの細胞表面に発現しているCD26と考えている。このCD26の発現上昇は過剰な炎症に繋がりうる。そこでCD26活性を抑制しうるDPP4阻害薬であるシタグリプチンにARDS抗炎症作用があるかどうかを、マウスモデルおよびヒト肺細胞を使用して研究した。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Involvement of pulmonary arteriopathy in the development and severity of reperfusion pulmonary endarterectomy.2019
Author(s)
Sanada TJ, Tanabe N, Ishibashi-Ueda H, Ishida K, Naito A, Sakao S, Suda R, Kasai H, Nishimura R, Sugiura T, Shigeta A, Taniguchi Y, Masuda M, Tatsumi K.
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Journal Title
Pulm Circ.
Volume: 9
Issue: 2
Pages: 1-9
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] S100A12 inhibits fibroblast migration via the receptor for advanced glycation end products and p38 MAPK signaling.2019
Author(s)
Tanaka N, Ikari J, Anazawa R, Suzuki M, Katsumata Y, Shimada A, Suzuki E, Matsuura Y, Kawata N, Tada Y, Tatsumi K.
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Journal Title
In Vitro Cell Dev Biol Anim
Volume: 55
Issue: 8
Pages: 656-664
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor.2018
Author(s)
Naito A, Sakao S, Lang IM, Voelkel NF, Jujo T, Ishida K, Sugiura T, Matsumiya G, Yoshino I, Tanabe N, Tatsumi K.
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Journal Title
BMC Pulm Med
Volume: 18
Issue: 1
Pages: 197-207
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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