PDGFR Upregulates HMGA1 Expression in the P53 Pathway to Facilitate Epidermal Differentiation of Adipose-Derived Mesenchymal Stem Cells

Author(s): Yan-Hong Wu, Jian-Wu Chen, Yu-Zhi Wang, Peng Liu, Zhong-Shan Wang, Xiao-Qiang Chen

Background: During the healing process, platelet-derived growth factor (PDGF) stimulates the regeneration of damaged tissue by interacting with PDGF receptor (PDGFR). This research seeks to investigate how PDGFR promotes the differentiation of adipose-derived mesenchymal stem cells (ADMSCs) into epidermal cells. Methods: ADMSCs were initially induced to differentiate into epidermal cells using an epidermal cell induction medium. Following the induction, cell morphology was examined microscopically, and immunofluorescence was employed to assess the fluorescence intensity of epidermal cell markers CK19 and CK10. Subsequently, cells were transfected with oe-PDGFR and exposed to the PDGF inducer PDGF-BB. Western blot and qPCR were used to determine PDGFR levels in the mRNA and protein. Cell proliferation and migration were evaluated through CCK-8 and Transwell assays.The expression levels of CK19 and CK10 was further analyzed via Western blot. In addition, bioinformatics analysis of RNA sequences were conducted to find out potential downstream targets and elucidate the molecular mechanisms. Results: Upon culturing in the epidermal cell medium, ADMSCs transformed from spindle-shaped to round or oval forms, were arranged in a cobblestone pattern, and exhibited high expression levels of CK19 and CK10. PDGFR expression was significantly increased following transfection with oe-PDGFR. Notably, the increased expression of PDGFR significantly enhanced cell proliferation and migration, elevated the expression levels of CK19 and CK10, and activated the ERK and AKT signaling pathways. The study combined bioinformatics analysis with in vitro rescue experiments, confirming that PDGFR overexpression upregulated HMGA1 expression. The inhibition of p53 activation facilitates differentiation of ADMSCs into epidermal cells. Conclusion: We found that PDGFR activated HMGA1, stimulating differentiation of ADMSCs by modulating the p53 signaling pathway in a way that facilitates their differentiation into epidermal cells.