2011 Fiscal Year Final Research Report
Identification of paracrine factors from mesenchaymal stem cell for protection and treatment against lung injury
Project/Area Number |
21590980
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Tohoku University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
NUKIWA Toshihiro 東北大学, 大学院・医学系研究科, 名誉教授 (40129036)
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Co-Investigator(Renkei-kenkyūsha) |
SAIJO Yasuo 新潟大学, 医学(系)研究科(研究院), 教授 (10270828)
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Project Period (FY) |
2009 – 2011
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Keywords | 間葉系幹細胞 / Stanniocalcin1 / アポトーシス / 過酸化ストレス / Uncoupling Protein 2 / 嫌気性代謝 / Warburg効果 / 肺胞細胞 |
Research Abstract |
Previous studies have demonstrated that mesenchymal stromal cells(MSCs)enhance cell survival through upregulation and secretion of stanniocalcin-1(STC1). This study shows that MSC-derived STC1 promotes survival of lung cancer cells by uncoupling oxidative phosphorylation, reducing intracellular reactive oxygen species(ROS), and shifting metabolism towards a more glycolytic metabolic profile. MSC-derived STC1 upregulated uncoupling protein 2(UCP2)in injured A549 cells in an STC1-dependent manner. Knockdown of UCP2 reduced the ability of MSCs and recombinant STC1(rSTC1)to reduce cell death in the A549 population. rSTC1-treated A549 cells displayed decreased levels of ROS, mitochondrial membrane potential(MMP), and increased lactate production, all of which were dependent on the upregulation of UCP2. Our data suggest that MSCs can promote cell survival by regulating mitochondrial respiration via STC1.
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