ERK1/2 and Akt phosphorylation were essential for MGF E peptide regulating cell morphology and mobility but not proangiogenic capacity of BMSCs under severe hypoxia

作者：Sha, Yongqiang; Yang, Li; Lv, Yonggang^*

来源：Cell Biochemistry and Function, 2018, 36(3): 155-165.

DOI：10.1002/cbf.3327

• adhesion
• BMSCs
• hypoxia
• MGF E peptide
• migration
• proangiogenic capacity

Severe hypoxia inhibits the adhesion and mobility of bone marrow-derived mesenchymal stem cells (BMSCs) and limits their application in bone tissue engineering. In this study, CoCl2 was used to simulate severe hypoxia and the effects of mechano-growth factor (MGF) E peptide on the morphology, adhesion, migration, and proangiogenic capacity of BMSCs under hypoxia were measured. It was demonstrated that severe hypoxia (500-M CoCl2) significantly caused cell contraction and reduced cell area, roundness, adhesion, and migration of BMSCs. RhoA and ROCK1 expression levels were upregulated by severe hypoxia, but p-RhoA and mobility-relevant protein (integrin 1, p-FAK and fibronectin) expression levels in BMSCs were inhibited. Fortunately, MGF E peptide could restore all abovementioned indexes except RhoA expression. MEK-ERK1/2 pathway was involved in MGF E peptide regulating cell morphological changes, mobility, and relevant proteins (except p-FAK). PI3K-Akt pathway was involved in MGF E peptide regulating cell area, mobility, and relevant proteins. Besides, severe hypoxia upregulated vascular endothelial growth factor expression but was harmful for proangiogenic capacity of BMSCs. Our study suggested that MGF E peptide might be helpful for the clinical application of tissue engineering strategy in bone defect repair. @@@ Significance of the studySever hypoxia impairs bone defect repair with bone marrow-derived mesenchymal stem cells (BMSCs). This study proved that mechano-growth factor E (MGF E) peptide could improve the severe hypoxia-induced cell contraction and decline of cell adhesion and migration of BMSCs. Besides, MGF E peptide weakened the effects of severe hypoxia on the cytoskeleton arrangement- and mobility-relevant protein expression levels in BMSCs. The underlying molecular mechanism was also verified. Finally, it was confirmed that MGF E peptide showed an adverse effect on the expression level of vascular endothelial growth factor in BMSCs under severe hypoxia but could make up for this deficiency through accelerating cell proliferation.

• 出版日期2018-4
• 单位重庆大学