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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

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Abstract

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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Acknowledgments

This study was supported by grants from the Key Science and Technology Planning Project of Fujian Province, China (Grant #2009I0022), the National Natural Science Foundation of China (Grant #81070473), and the Medical Science and Technology Foundation of the Military Region (Grant #08MA099).

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Authors and Affiliations

  1. Fuzong Clinical College, Fujian Medical University, Fuzhou, 350025, Fujian, China

    Chunjing Chen & Yanfeng Song

  2. 476th Clinical Department of Fuzhou General Hospital, Fuzhou, China

    Ying Xu

  3. Department of Obstetrics and Gynecology, Fuzhou General Hospital, Fuzhou, 350025, Fujian, China

    Yanfeng Song

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  1. Chunjing Chen
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  2. Ying Xu
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  3. Yanfeng Song
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Correspondence to Yanfeng Song.

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Chen, C., Xu, Y. & Song, Y. 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. Mol Cell Biochem 386, 167–175 (2014). https://doi.org/10.1007/s11010-013-1855-8

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  • DOI: https://doi.org/10.1007/s11010-013-1855-8

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