Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway

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dc.contributor.authorMahmoud Al-Azab
dc.contributor.authorBing Wang
dc.contributor.authorAbdalkhalig Elkhider
dc.contributor.authorWilliams Walana
dc.contributor.authorWeiping Li1
dc.contributor.authorBo Yuan
dc.contributor.authorYunshan Ye
dc.contributor.authorYawei Tang
dc.contributor.authorMarwan Almoiliqy
dc.contributor.authorSalah Adlat
dc.contributor.authorJing Wei
dc.contributor.authorYan Zhang
dc.contributor.authorXia Li
dc.date.accessioned2023-01-02T08:06:34Z
dc.date.available2023-01-02T08:06:34Z
dc.date.issued2020-04-01
dc.description.abstractPremature senescence of bone marrow-derived mesenchymal stem cells (BMSC) remains a major concern for their application clinically. Hedgehog signaling has been reported to regulate aging-associated markers and MSC skewed differentiation. Indian Hedgehog (IHH) is a ligand of Hedgehog intracellular pathway considered as an inducer in chondrogenesis of human BMSC. However, the role of IHH in the aging of BMSC is still unclear. This study explored the role IHH in the senescence of BMSC obtained from human samples and senescent mice. Isolated BMSC were transfected with IHH siRNA or incubated with exogenous IHH protein and the mechanisms of aging and differentiation investigated. Moreover, the interactions between IHH, and mammalian target of rapamycin (mTOR) and reactive oxygen species (ROS) were evaluated using the corresponding inhibitors and antioxidants. BMSC transfected with IHH siRNA showed characteristics of senescence-associated features including increased senescence-associated β-galactosidase activity (SA-β-gal), induction of cell cycle inhibitors (p53/p16), development of senescence-associated secretory phenotype (SASP), activation of ROS and mTOR pathways as well as the promotion of skewed differentiation. Interestingly, BMSC treatment with IHH protein reversed the senescence markers and corrected biased differentiation. Moreover, IHH shortage-induced senescence signs were compromised after mTOR and ROS inhibition. Our findings presented anti-aging activity for IHH in BMSC through down-regulation of ROS/mTOR pathways. This discovery might contribute to increasing the therapeutic, immunomodulatory and regenerative potency of BMSC and introduce a novel remedy in the management of aging-related diseases.
dc.identifier.citationAl-Azab, M., Wang, B., Elkhider, A., Walana, W., Li, W., Yuan, B., Ye, Y., Tang, Y., Almoiliqy, M., Adlat, S. and Wei, J., 2020. Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway. Aging (Albany NY), 12(7), p.5693.
dc.identifier.urihttp://dspace.napata.edu.sd/handle/123456789/175
dc.language.isoen
dc.titleIndian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway
dc.typeArticle
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