Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of plastic and reconstructive surgery, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian, China.
Int J Med Sci. 2024 Sep 23;21(13):2480-2493. doi: 10.7150/ijms.97885. eCollection 2024.
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. We transfected 3T3-L1 preadipocytes with PPARγ-modRNA to investigate adipogenic differentiation and cellular proliferation . , 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. PPARγ-modRNA significantly enhanced adipogenesis and proliferation in 3T3-L1 preadipocytes . The injection of PPARγ-modified mRNA led to accelerated wound healing compared to the control groups . 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. 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.
脂肪细胞在组织再生中起着至关重要的作用，有助于受损区域的恢复，并调节炎症环境。通过化学修饰过的过氧化物酶体增殖物激活受体γ mRNA（PPARγ-modRNA）来调节基因表达，为精确控制脂肪生成过程提供了一种复杂的方法。本研究旨在探讨 PPARγ-modRNA 在 3T3-L1 前脂肪细胞中的成脂潜能及其在伤口愈合中的作用。我们将 PPARγ-modRNA 转染到 3T3-L1 前脂肪细胞中，以研究脂肪生成分化和细胞增殖。接着，我们采用了一种鼠全层皮肤缺损模型，比较了 modRNA 介导的过氧化物酶体增殖物激活受体γ过表达与对照组的效果。此外，我们对荧光素酶修饰的 mRNA（LUC）和 PPARγ-modRNA 转染细胞（PPAR）进行了 RNA 测序，以全面了解分子机制。PPARγ-modRNA 显著增强了 3T3-L1 前脂肪细胞的脂肪生成和增殖。与对照组相比，PPARγ 修饰 mRNA 的注射加速了伤口愈合。RNA 测序显示，PPAR 组中与脂肪生成相关的基因上调，特别是与 TNF 信号通路相关的基因。随后，KEGG 分析表明，modRNA 介导的过氧化物酶体增殖物激活受体γ过表达有效地促进了脂肪生成，同时抑制了 TNF-α 介导的炎症和细胞凋亡。本研究证明了 PPARγ-modRNA 诱导脂肪生成和加速伤口愈合的创新性应用。通过 modRNA 技术实现的过氧化物酶体增殖物激活受体γ核表达是一项显著的进展，为未来针对脂肪生成过程和炎症抑制的治疗策略提供了新的思路，特别是在伤口愈合方面。
