期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 476, 期 4, 页码 1705-1716出版社
SPRINGER
DOI: 10.1007/s11010-020-04033-w
关键词
ADSCs; Adipogenic differentiation; miR-26a; PPAR gamma; CDK5; FOXC2
类别
资金
- National Natural Science Foundation of China [81660153, 81660141]
- Joint Research Found of Yunnan Provincial Science and Technology Department-Kunming Medical University [2017FE468-197]
The study demonstrates that miR-26a regulates insulin-induced adipogenic differentiation of ADSCs by modulating the CDK5/FOXC2 pathway, providing insights into the mechanistic understanding of obesity and type 2 diabetes.
Objective: Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes, since insulin can induce adipogenic differentiation of human adipose-derived stem cells (ADSCs). MiR-26a was reported to be highly expressed in ADSCs under induction and Forkhead box C2 (FOXC2), as a key substrate of cyclin-dependent kinase 5 (CDK5) could inhibit white adipocyte differentiation, which was mediated by miR-26a. However, the relationship between miR-26a and CDK5/FOXC2 during ADSCs differentiation remains unknown. We want to verify the regulated mechanism of miR-26a/CDK5/FOXC2 axis participating in the adipogenic differentiation of ADSCS. Methods: ADSCs were isolated and verified by flow cytometry. Oil Red O staining was performed to assess the capacity for adipogenic differentiation of ADSCs. The proliferation ability of ADSCs was verified by MTT assay. The expression of miR-26a, peroxisome proliferator-activated receptors gamma (PPAR gamma), CDK5, and FOXC2 were tested by qRT-PCR and Western blot, and the relationship between miR-26a and CDK5 was verified by dual-luciferase reporter gene assay. Results: MiR-26a and PPAR gamma were upregulated and CDK5 and FOXC2 were downregulated during adipogenic differentiation of ADSCs. Knockdown of miR-26a or overexpression of CDK5 could inhibit adipogenic differentiation of ADSCs induced by insulin. MiR-26a could directly target CDK5 and the effect of miR-26a inhibitor on adipogenic differentiation of ADSCs could be blocked by si-CDK5. Conclusion: We demonstrated that miR-26a regulated insulin-induced adipogenic differentiation of ADSCs by regulating CDK5/FOXC2 pathway, which could provide the key to a comprehensive mechanistic understanding of obesity and type 2 diabetes.
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