LincRNA-p21 promotes mesenchymal stem cell migration capacity and survival through hypoxic preconditioning

作者：Shanshan Meng, Xiuping Xu, Wei Chang, Zhonghua Lu, Lili Huang, Jingyuan Xu, Ling Liu, Haibo Qiu, Yi Yang, Fengmei Guo · 发表于：Stem Cell Research & Therapy · 年份：2018 · DOI：10.1186/s13287-018-1031-x · 被引用次数：120 · 研究领域：Mesenchymal stem cell research、Cancer, Hypoxia, and Metabolism、MicroRNA in disease regulation

BACKGROUND: Mesenchymal stem cells (MSCs) derived from bone marrow have potent stabilizing effects for the treatment of acute respiratory distress syndrome (ARDS). However, low efficiency and survival in MSC homing to injured lung tissue remains to be solved. Therefore, the aim of this study was to assess whether large intergenic noncoding RNA (LincRNA)-p21 promote MSC migration and survival capacity through hypoxic preconditioning in vitro. METHODS: MSCs were cultured and divided into the normoxia culture group (20% O2) and hypoxia culture group (1% O2). To determine roles and mechanisms, lentivirus vector-mediated LincRNA-p21 knockdown of MSCs and hypoxia-inducible factor (HIF-1α) inhibitor KC7F2 were introduced. Additionally, MSC migration was analyzed by scratch test and transwell migration assays. MSC proliferation was tested by cell counting kit-8 and trypan blue dye. Apoptosis was detected by Annexin V-PE/7-AAD stained flow cytometry. Moreover, LincRNA-p21 and HIF-1α mRNA was measured by reverse transcription-polymerase chain reaction, and HIF-1α and CXCR4/7 protein were assayed by western blot (WB) or enzyme-linked immunosorbent assay (ELISA). Apoptosis protein caspase-3 and cleaved-caspase-3 were investigated by WB analysis. Considering interactions between VHL and HIF-1α under LincRNA-p21 effect, co-immunoprecipitation was detected. RESULTS: Hypoxic preconditioning MSC promoted migration capacity and MSC survival than normoxia culture group. MSCs induced by hypoxic ...