Hypoxia induces autophagy of bone marrow-derived mesenchymal stem cells via activation of ERK1/2.

ABSTRACT

BACKGROUND: Bone marrow-derived mesenchymal stem cells (bmMSCs) are the most promising seed cells for cell transplant therapy. Hypoxia is a known stimulus of autophagy. Recent studies showed that hypoxia promotes autophagy of human placental chorionic plate-derived mesenchymal stem cells (CP-MSCs). However, whether hypoxia affects autophagy of bmMSCs has not been examined. The goal of this study was to investigate the effect of hypoxia on autophagy of mouse bmMSCs and the underlying mechanisms. METHODS: BmMSCs from mouse bone marrow were randomly divided into three groups control (C), hypoxia (H) and hypoxia + reoxygenation (H+R) groups. Subsequent autophagic signals were analyzed by immunostaining and Western blot assays. RESULTS: The expression of autophagic signals LC-3, Atg5 and Beclin-1, as well as the conversion of LC3B-I to LC3B-II in bmMSCs were significantly increased in H group as compared with control (p<0.05). These autophagic signals were also higher in H+R group than in H group (p<0.05). Also, the expression of phospho-ERK1/2 was significantly increased in H and H+R groups as compared with control (p<0.05). Notably, application of ERK1/2 inhibitor U0126 (5µM) significantly repressed hypoxia-induced expression of LC-3 and Atg5, as well as conversion of LC3B-I to LC3B-II (p<0.05). CONCLUSION: Hypoxia can induce autophagy of bmMSCs, which depends on activation of ERK1/2 pathway.