Hyaluronic Acid Hydrogel Inhibits Autophagy Through the miR-181a-5p/ATG5 Molecular Axis to Promote the Adipogenic Differentiation of Adipose-Derived Stem Cells

Background Soft tissue defects refer to defects in or damage to human soft tissue, which may affect the appearance, function, and health of the human body and cause physical and psychological distress to the patient. Hyaluronic acid (HA), a fillable material in the field of plastic medicine, could play a crucial role in reconstructing soft tissues and enhancing the adipogenic differentiation of adipose-derived stem cells (ADSCs). Methods We isolated ADSCs from human subcutaneous adipose tissue and cultured them in HA hydrogel at a density of 2.1 × 10 6 /mL, followed by subcutaneous injections of ADSCs (0.2 mL, 1 × 10 7 cells/mL with 0.2 mL of DMEM) and HA hydrogel (0.2 mL) into the dorsal side of nude mice. The expression of related genes and proteins was detected using RT‒qPCR and western blotting. The adipogenic differentiation of ADSCs and adipogenesis in nude mice were assessed using CCK-8, Oil Red O, and HE staining. Results The results revealed an increase in the levels of miR-181a-5p and adipocyte differentiation-related proteins (PPARγ, C/EBPα, FABP4, and adiponectin) and a decrease in the levels of autophagy-related proteins (LC3II/I, Beclin-1, and ATG5) in ADSCs cocultured with HA hydrogel. The adipogenic differentiation ability of ADSCs was enhanced. From a mechanistic standpoint, HA hydrogel inhibited the expression of ATG5 by promoting the expression of miR-181a-5p, thus inhibiting autophagy, promoting the adipogenic differentiation of ADSCs, and promoting the formation of adipose tissue in vivo. Conclusions Our findings suggest that a combined culture of ADSCs and HA hydrogel may be a new method to enhance the adipogenic differentiation of ADSCs.