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Min Wang, Guangxin Yang, Xiaoyan Jiang, Debin Lu, Hao Mei, Bing Chen
(Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing, China (mainland))
Med Sci Monit 2017; 23:3451-3460
To study the effect of estrogen-related receptor α (ERRα) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) on mesenchymal stem cells (MSCs) apoptosis, and further investigated its detailed molecular mechanisms in the absence of serum, hypoxia, and high glucose conditions.
MATERIAL AND METHODS: In our study, we first evaluated the expression rates of CD14, CD34, CD45, CD44, CD29, and Sca-1 surface markers on MSCs by flow cytometry. Then, the ability of osteogenic and fatty differentiation of MSCs was determined by osteogenic differentiation and adipogenesis reagent kit. Next, Annexin V-APC/7-AAD apoptosis kit was used for detecting the apoptosis rate of MSCs. RT-PCR and Western blotting were used for detection of mRNA expression and proteins expression, respectively.
RESULTS: Our data showed that the MSCs used in our study were capable of self-renewal and differentiating into many cell lineages, such as osteogenic differentiation and adipogenesis. Our results further showed that over-expression of PGC-1α could protect MSCs from apoptosis induced by rotenone. We also found that PGC-1α over-expression could enhance the expression of anti-apoptotic gene Bcl-2, and inhibit the expression of pro-apoptotic gene Bax in MSCs. In addition, our data demonstrated that PGC-1α could induce upregulation of Bcl-2 and further promote the survival of MSCs by interacting with ERRα.
CONCLUSIONS: In the absence of serum, hypoxia and high glucose conditions, PGC-1α can regulate the expression of Bcl-2 and promote the survival of MSCs via PGC-1α/ERRα interaction.