Chemically Modified PPARγ mRNA Unleashes Adipogenic Potential in 3T3-L1-Predipocytes: An Approach for Accelerated...

Background: Adipocytes play a crucial role in tissue regeneration, contributing to the restoration of damaged areas and modulating the inflammatory milieu. The modulation of gene expression through chemically modified PPARγ mRNA (PPARγ-modRNA) introduces a sophisticated approach to precisely control adipogenic processes. This study aims to explore the adipogenic potential of the PPARγ-modRNA in 3T3-L1 preadipocytes and its role in wound healing. Materials and Methods: We transfected 3T3-L1 preadipocytes with PPARγ-modRNA to investigate adipogenic differentiation and cellular proliferation in vitro. In vivo, we employed a murine full-thickness skin defect model and compared the effects of modRNA-mediated PPARγ overexpression with control groups. Additionally, we conducted RNA sequencing on luciferase-modified mRNA (LUC) and PPARγ-modRNA-transfected cells (PPAR) for a comprehensive understanding of molecular mechanisms. Results: PPARγ-modRNA significantly enhanced adipogenesis and proliferation in 3T3-L1 preadipocytes in vitro. The injection of PPARγ-modified mRNA led to accelerated wound healing compared to the control groups in vivo. RNA sequencing revealed upregulation of adipogenesis-related genes in the PPAR group, notably associated with the TNF signaling pathway. Subsequently, the KEGG analysis indicated that modRNA-mediated PPARγ overexpression effectively promoted adipogenesis while inhibiting TNF-α-mediated inflammation and cellular apoptosis. Conclusions: This study demonstrates the innovative use of PPARγ-modRNA to induce adipogenesis and expedite wound healing. The nuclear expression of PPARγ through modRNA technology signifies a notable advancement, with implications for future therapeutic strategies targeting adipogenic processes and the inhibition of inflammation in the context of wound healing.