title: Hypoxia inducible factor 1α promotes survival of mesenchymal stem cells under hypoxia.
abstract: Mesenchymal stem cells (MSCs) are ideal materials for cell therapy. Research has indicated that hypoxia benefits MSC survival, but little is known about the underlying mechanism. This study aims to uncover potential mechanisms involving hypoxia inducible factor 1α (HIF1A) to explain the promoted MSC survival under hypoxia. MSCs were obtained from Sprague-Dawley rats and cultured under normoxia or hypoxia condition. The overexpression vector or small interfering RNA ofHif1agene was transfected to MSCs, after which cell viability, apoptosis and expression of HIF1A were analyzed by MTT assay, flow cytometry, qRT-PCR and Western blot. Factors in p53 pathway were detected to reveal the related mechanisms. Results showed that hypoxia elevated MSCs viability and up-regulated HIF1A (P< 0.05) as previously reported. HIF1A overexpression promoted viability (P< 0.01) and suppressed apoptosis (P< 0.001) under normoxia. Correspondingly, HIF1A knockdown inhibited viability (P< 0.05) and promoted apoptosis (P< 0.01) of MSCs under hypoxia. Expression analysis suggested that p53, phosphate-p53 and p21 were repressed by HIF1A overexpression and promoted by HIF1A knockdown, and B-cell CLL/lymphoma 2 (BCL2) expression had the opposite pattern (P< 0.05). These results suggest that HIF1A may improve viability and suppress apoptosis of MSCs, implying the protective effect of HIF1A on MSC survival under hypoxia. The underlying mechanisms may involve the HIF1A-suppressed p53 pathway. This study helps to explain the mechanism of MSC survival under hypoxia, and facilitates the application of MSCs in cell therapy.
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University; The National Key Clinical Specialty; The Engineering Technology Research Center of Education Ministry of China; Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Guangzhou 510282, China.
authors.forename: Bingke
authors.initials: B
authors.lastname: Lv
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University; The National Key Clinical Specialty; The Engineering Technology Research Center of Education Ministry of China; Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Guangzhou 510282, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University; The National Key Clinical Specialty; The Engineering Technology Research Center of Education Ministry of China; Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Guangzhou 510282, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University; The National Key Clinical Specialty; The Engineering Technology Research Center of Education Ministry of China; Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Guangzhou 510282, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University; The National Key Clinical Specialty; The Engineering Technology Research Center of Education Ministry of China; Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Guangzhou 510282, China.
authors.forename: Chengmei
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University; The National Key Clinical Specialty; The Engineering Technology Research Center of Education Ministry of China; Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Guangzhou 510282, China.
authors.forename: Jianbang
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University; The National Key Clinical Specialty; The Engineering Technology Research Center of Education Ministry of China; Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Guangzhou 510282, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Hua
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University; The National Key Clinical Specialty; The Engineering Technology Research Center of Education Ministry of China; Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Guangzhou 510282, China.
authors.forename: Zhongfei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University; The National Key Clinical Specialty; The Engineering Technology Research Center of Education Ministry of China; Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Guangzhou 510282, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University; The National Key Clinical Specialty; The Engineering Technology Research Center of Education Ministry of China; Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Guangzhou 510282, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Jiang
keywords: Hypoxia inducible factor 1α; apoptosis; hypoxia; mesenchymal stem cell; p53