• igf-1 gene-modified muscle-derived stem cells are resistant to oxidative stress via enhanced activation of igf-1r/pi3k/akt signaling and secretion of vegf

    جزئیات بیشتر مقاله
    • تاریخ ارائه: 1392/07/24
    • تاریخ انتشار در تی پی بین: 1392/07/24
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     reactive oxygen species (ros)-induced oxidative stress increases in skeletal muscle with aging and decreases the viability of implanted cells. type 1 insulin-like growth factor (igf-1) promotes the survival of skeletal muscle cells under oxidative stress. it is unknown whether igf-1 protects muscle-derived stem cells (mdscs) from oxidative stress. in this study, we genetically engineered rat mdscs to overexpress igf-1 and determined cell viability, apoptosis, and vegf secretion under oxidative stress. overexpression of igf-1 prevented mdscs from h2o2-induced caspase-dependent apoptotic cell death by upregulating the pi3k/akt pathway, accompanied with an increase of nf-κb, p-nf-κb, bcl-2, and vegf, as well as a decrease of bax. in contrast, pre-administration of picropodophyllinb, wortmannin, 1l-6-hydroxymethyl-chiro-inositol-2-((r)-2-o-methyl-3-o-octadecylcarbonate), or pyrrolidine-dithiocarbamate, specific inhibitors of igf-1r, pi3k, akt, and nf-κb, respectively, followed by treatment with h2o2, resulted in cell death of mdscs. our data indicated that igf-1 suppresses apoptosis and enhances the paracrine function of mdscs under oxidative stress via enhancing igf-1r/pi3k/akt signaling. thus, igf-1 gene-modified mdscs present a potential application in the treatment of muscle wasting, such as urethra intrinsic sphincter deficiency.

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