國家衛生研究院 NHRI:Item 3990099045/10735
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    题名: 5-methoxytryptophan protects MSCs from stress induced premature senescence by upregulating FoxO3a and mTOR
    作者: Chang, TC;Hsu, MF;Shih, CY;Wu, KK
    贡献者: Institute of Cellular and Systems Medicine
    摘要: 5-methoxytryptophan (5-MTP) is a newly discovered tryptophan metabolite which controls stress-induced inflammatory signals. To determine whether 5-MTP protects against stress-induced mesenchymal stem cell (MSC) senescence, we incubated bone marrow-derived MSC (BM-MSC) in high-glucose medium or regular medium for 2 weeks followed by addiction of 5-MTP (10 muM) or vehicle for 48 h. 5-MTP reduced p16 and p21 expression, senescence-associated beta-Gal (SA-beta-Gal) and IL-6 secretion and increased BrdU incorporation. 5-MTP exerted a similar effect on BM-MSC senescence induced by a sublethal concentration of H2O2. 5-MTP enhanced FoxO3a expression and increased superoxide dismutase and catalase activities in HG BM-MSCs. Silencing of FoxO3a with siRNA abrogated 5-MTP-mediated reduction of SA-beta-Gal and IL-6 secretion but not p21 or p16. Since mechanistic target of rapamycin (mTOR) is involved in cellular senescence, we determined whether 5-MTP influences mTOR expression. Our data reveal that mTOR protein level was depressed in HG-MSC which was rescued by 5-MTP. Rapamycin abrogated 5-MTP-mediated suppression of p16, p21, SA-beta-Gal and IL-6 and rise of BrdU incorporation. Our findings suggest that 5-MTP protects MSCs against stress-induced senescence via FoxO3a and mTOR upregulation and has potential to improve cell expansion for cell therapy.
    日期: 2017-09-11
    關聯: Scientific Reports. 2017 Sep 11;7:Article number 11133.
    Link to: http://dx.doi.org/10.1038/s41598-017-11077-4
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2045-2322&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000410063400062
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85029285782
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