Hypoxia preconditioning promotes bone marrow mesenchymal stem cells survival and vascularization through the activation of hif-1α/malat1/vegfa pathway
10.3969/j.issn.2095-4344.2160
- Author:
Jingying HOU
1
Author Information
1. Emergency Department, Sun Yat-sen Memorial Hospital of Sun Yat-sen University
- Publication Type:Journal Article
- Keywords:
Bone marrow mesenchymal stem cells;
Hypoxia induced factor-1α;
Hypoxia preconditioning;
Long non-coding RNA;
Metastasis-associated lung adenocarcinoma transcript 1;
Stem cells;
Vascular endothelial growth factor A;
Vascularization
- From:
Chinese Journal of Tissue Engineering Research
2021;25(7):985-990
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Previous study demonstrated that hypoxia preconditioning promoted mesenchymal stem cells survival and their therapeutic efficacy, and this effect was mediated by hypoxia induced factor-1α (HIF-1α). However, specific downstream mechanism remained unclear. OBJECTIVE: To observe the influence of hypoxia preconditioning on the survival and vascularization potential of bone marrow mesenchymal stem cells in vitro and explore the regulatory mechanism of HIF-1α/MALAT1/VEGFA pathway. METHODS: Bone marrow mesenchymal stem cells were obtained and cultured in vitro. Cells were divided into hypoxia (1% O2) and normoxia control groups (20% O2), and cultured for 24 hours. Cells proliferation, apoptosis and vascularization were evaluated. The expression of HIF-1α, MALAT1, and VEGFA was detected. HIF-1α and MALAT1 were inhibited by their siRNAs separately. HIF-1α siRNA scramble and MALAT1 siRNA scramble were used as negative controls before hypoxia preconditioning. Alterations of the molecules were examined and compared in different groups. RESULTS AND CONCLUSION: (1) Compared with the normoxia control group, cell viability was significantly enhanced; and cell apoptosis percentage was significantly declined in the hypoxia group; vascular lumen like structure was also increased significantly in the hypoxia group (P < 0.01); expression of HIF-1α, MALAT1, and VEGFA was significantly increased in the hypoxia group (P < 0.01). (2) After the inhibition of HIF-1α and hypoxia preconditioning, both MALAT1 and VEGFA expression levels were significantly reduced (P < 0.01). The expression of VEGFA was also significantly suppressed after the blockage of MALAT1 (P < 0.01). (3) This study suggested that hypoxia preconditioning effectively promoted bone marrow mesenchymal stem cell survival and vascularization through the activation of HIF-1α/MALAT1/VEGFA pathway.
