MiR-26a regulated adipogenic differentiation of ADSCs induced by insulin through CDK5/FOXC2 pathway

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.

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 γ (PPARγ), 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.

MiR-26a and PPARγ 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.

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.