Heregulin-1β Promotes the Synergistic Effect Between Allogenic Skin-Derived Precursor Differentiated Schwann Cells (SKP-SC) and Acellular Nerve Allograft (ANA) in Peripheral Nerve Regeneration Through Inhibiting Mir-21

Previous studies in our lab found that heregulin-1β with SKP-SCs (neurons and Schwann cells differentiated from SKPs) / ANA (acellular nerve allograft) transplantation represented a powerful therapeutic approach, and facilitates the efficacy of ANA in peripheral nerve injury. In this study, our purpose is to explore the mechanism between them. Firstly we transplanted ANA + SKP-SC + heregulin-1β into rats with right sciatic nerve injury and then detected the miR-21 and SOX2 (SRY-like HMG box 2) levels. Then we transfected miR-21 inhibitor in SCs (Schwann cells) which induced in hypoxic condition before harvesting. Then we detected expression of miR-21 and SOX2 using real time-PCR and western blot assay. Results in vivo showed that the expression of miR-21 in rats was inhibited after transplantation of ANA + SKP-SC + heregulin-1β with induced SOX2 accordingly. Then we found miR-21 was increased time dependently in hypoxic SCs with decreased SOX2 accordingly. After miR-21 inhibitor transfection, miR-21 level was reduced and SOX2 was up-regulated. Meanwhile it was also showed that the miR-21 inhibitor induced the hypoxic SCs growth, decreased the apoptosis with cell cycle changing. In conclusion miR-21 and its target gene SOX2 played important role in peripheral nerve injury. Heregulin-1β may increase the synergistic effect between SKP-SC and ANA through inhibiting miR-21 in vivo.

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