Skin wound repairing effects of adipose mesenchymal stem cells is promoted by the combined application of insulin-like growth factor 1: The key role of miR-21-5p-mediated signaling transduction.

ABSTRACT

Mesenchymal stem cells (ADMSCs) have been applied to the treatment of skin injuries and the co-administration of cytokines can enhance the effects. In the current study, the promoting effects of insulin-like growth factor 1 (IGF-1) on the skin wound healing effects of adipose-derived MSCs (ADMSCs) were assessed and the associated mechanism was explored by focusing on miR-21-5p mediated pathways. ADMSCs were isolated from epididymis rats, and skin wounded rats were employed as the in vivo model for evaluating the effect of ADMCs on skin healing and secretion of cytokines. Then a microarray assay was employed to select potential miR target of IGF-1 on ADMSCs. The level of the selected miR was modulated in ADMSCs, and the effects on skin injuries were also assessed. Administration of ADMSCs promoted skin wound healing and induced the production of bFGF, IL-1ß, PDGF, SDF-1, IGF-1, and TNF-α. The co-administration of IGF-1 and ADMSCs strengthened the effect of ADMSCs on skin wound by suppressing activity of matrix metalloproteinase-1 (MMP-1). At molecular level, the treatment of IGF-1 up-regulated miR-21-5p level in ADMSCs, which then suppressed the expression of KLF6 in injured skin tissues and promoted wound healing. The inhibition of miR-21-5p counteracted the promoting effects of IGF-1 on the skin healing effects of ADMSCs. Findings outlined in the current study indicated that IGF-1 could promote the wound healing effects of ADMSCs by up-regulating miR-21-5p level.