Hypoxia-inducible factor 1 α protects mesenchymal stem cells against oxygen-glucose deprivation-induced injury via autophagy induction and PI3K/AKT/mTOR signaling pathway

Am J Transl Res. 2017 May 15;9(5):2492-2499. eCollection 2017.


Mesenchymal stem cell (MSC) transplantation is a promising therapeutic strategy for myocardial infarction. The survival rate of the grafted MSCs is limited by the conditions of hypoxia and low nutrient levels. In this study, we investigated the role of hypoxia-inducible factor 1 alpha (Hif-1α) in oxygen-glucose deprivation (OGD)-induced injury in MSCs. Hif-1α was overexpressed or suppressed in MSCs by transfection with a Hif-1α expressing vector or Hif-1α-specific siRNA, respectively. Then MSCs were exposed to OGD, and the changes in cell viability, cell cycle distribution and apoptosis were respectively monitored by MTT assay and flow cytometry. Additionally, expression levels of Beclin1, LC3 I and LC3 II, as well phosphorylation of PI3K, AKT and mTOR were detected by RT-PCR and Western blotting. The results indicated that Hif-1α overexpression improved cell viability, reduced G1 phase cells accumulation, and suppressed apoptosis under OGD condition (P<0.05). Beclin1 expression and the LC3 II/LC3 I ratio were increased by Hif-1α overexpression, and were decreased by Hif-1α knock-down (P<0.05). In addition, PI3K, AKT and mTOR were inactivated by Hif-1α overexpression, and phosphorylated by Hif-1α knock-down (P<0.05). In conclusion, these data suggest that Hif-1α overexpression protects MSCs from OGD-induced injury via a mechanism in which autophagy and PI3K/AKT/mTOR pathway are implicated.

Keywords: Hif-1α; MSC; OGD; PI3K/AKT/mTOR pathway; autophagy.