Enhancing the ability of autophagy and proliferation of bone marrow mesenchymal stem cells by interleukin-8 through Akt-STAT3 pathway in hypoxic environment

Abstract

To study the effects and mechanisms of interleukin-8 (IL-8) on the proliferation and autophagy of human bone marrow mesenchymal stem cells (hBMSC) under hypoxic condition. In the hypoxia model, we set the non-stimulated hBMSC as the hypoxia control group; the hBMSC stimulated by 100 μmol/L human IL-8 as the IL-8 group; the hBMSC stimulated by 50 μmol/L MK2206 (Akt protein inhibitor) and 100μmol/L IL-8 as the Akt inhibitor group; and the normal cultured hBMSC as the normal control group. The experiments of EdU cell proliferation and TUNEL apoptosis were respectively used to detect the number of positive cells that were labeled by EdU and apoptosis in each group, and Western blotting and ELISA were used respectively to detect the expression of autophagy protein (LC-3), Akt/STAT3 and other proteins in each group. The results indicated that the proliferation and autophagy of hBMSC in IL-8 group was higher than that in hypoxia control group and Akt inhibitor group, and the apoptosis rate in IL-8 group decreased. These results and the high expression of Akt, STAT3 and VEGF protein of IL-8 group show that under the hypoxic condition, IL-8 played a protective role on MSC through the Akt-STAT3 pathway. It had important significance in the protection of MSC against the injury due to ischemia and hypoxia, and promoted the application of MSC in regenerative medicine.