Byun Kyung-A, Seo Suk Bae, Oh Seyeon, Jang Jong-Won, Son Kuk Hui, Byun Kyunghee
Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea.
LIBON Inc., Incheon 22006, Republic of Korea.
Int J Mol Sci. 2024 Nov 27;25(23):12739. doi: 10.3390/ijms252312739.
During aging, subcutaneous white adipose tissue (sWAT) thickness and the adipogenic potential of adipose-derived stem cells (ASCs) decline. Poly-D,L-lactic acid (PDLLA) fillers are commonly used to restore diminished facial volume. Piezo1 increases polarizing macrophages towards the M2 phenotype, which promotes the secretion of fibroblast growth factor 2 (FGF2), thereby increasing ASC survival. This study evaluated whether PDLLA enhances adipogenesis in ASCs by modulating M2 polarization in an in vitro senescence model and in aged animals. Lipopolysaccharide (LPS)-induced senescent macrophages showed decreased Piezo1, which was upregulated by PDLLA. CD163 (an M2 marker) and FGF2 were downregulated in senescent macrophages but were upregulated by PDLLA. We evaluated whether reduced FGF2 secretion from senescent macrophages affects ASCs by applying conditioned media (CM) from macrophage cultures to ASCs. CM from senescent macrophages decreased ERK1/2 and proliferation in ASCs, both of which were restored by CM from PDLLA-stimulated senescent macrophages. Adipogenesis inducers (PPAR-γ and C/EBP-α) were downregulated by CM from senescent macrophages but upregulated by CM from PDLLA-stimulated senescent macrophages in ASCs. Similar patterns were observed in aged animal adipose tissue. PDLLA increased Piezo1 activity, M2 polarization, and FGF2 levels. PDLLA also enhanced ERK1/2, cell proliferation, PPAR-γ, and C/EBP-α expression, leading to increased adipose tissue thickness. In conclusion, our study showed that PDLLA increased adipose tissue thickness by modulating adipogenesis.
在衰老过程中，皮下白色脂肪组织（sWAT）厚度以及脂肪来源干细胞（ASC）的成脂潜能会下降。聚-D,L-乳酸（PDLLA）填充剂常用于恢复减少的面部容积。Piezo1可使巨噬细胞向M2表型极化增加，这会促进成纤维细胞生长因子2（FGF2）的分泌，从而提高ASC的存活率。本研究评估了PDLLA是否通过在体外衰老模型和老年动物中调节M2极化来增强ASC的成脂作用。脂多糖（LPS）诱导的衰老巨噬细胞显示Piezo1减少，而PDLLA可使其上调。衰老巨噬细胞中CD163（一种M2标志物）和FGF2下调，但PDLLA可使其上调。我们通过将巨噬细胞培养的条件培养基（CM）应用于ASC来评估衰老巨噬细胞中FGF2分泌减少是否会影响ASC。衰老巨噬细胞的CM降低了ASC中的ERK1/2和增殖，而PDLLA刺激的衰老巨噬细胞的CM可使其恢复。衰老巨噬细胞的CM下调了ASC中的成脂诱导剂（PPAR-γ和C/EBP-α），但PDLLA刺激的衰老巨噬细胞的CM可使其上调。在老年动物脂肪组织中也观察到了类似的模式。PDLLA增加了Piezo1活性、M2极化和FGF2水平。PDLLA还增强了ERK1/2、细胞增殖、PPAR-γ和C/EBP-α的表达，导致脂肪组织厚度增加。总之，我们的研究表明PDLLA通过调节成脂作用增加了脂肪组织厚度。
