INSERM UMR_S 976, Skin Research Center, Saint-Louis Hospital, Paris, France.
Paris University, Paris Cité, Paris, France.
Aging (Albany NY). 2024 Aug 27;16(16):11776-11795. doi: 10.18632/aging.206055.
Crucial for skin homeostasis, synthesis and degradation of extracellular matrix components are orchestrated by dermal fibroblasts. During aging, alterations of component expression, such as collagens and enzymes, lead to reduction of the mechanical cutaneous tension and defects of skin wound healing. The aim of this study was to better understand the molecular alterations underwent by fibroblasts during aging by comparing secretomic and proteomic signatures of fibroblasts from young (<35years) and aged (>55years) skin donors, in quiescence or TGF-stimulated conditions, using HLPC/MS. The comparison of the secretome from young and aged fibroblasts revealed that 16 proteins in resting condition, and 11 proteins after a 24h-lasting TGF-β1-treatment, were expressed in significant different ways between the two cell groups (fold change>2, <0.05), with a 77% decrease in the number of secreted proteins in aged cells. Proteome comparison between young and aged fibroblasts identified a significant change of 63 proteins in resting condition, and 73 proteins in TGF-β1-stimulated condition, with a 67% increase in the number of proteins in aged fibroblasts. The majority of the differentially-expressed molecules belongs to the cytoskeleton-associated proteins and aging was characterized by an increase in Coronin 1C (CORO1C), and Filamin B (FLNB) expression in fibroblasts together with a decrease in Cofilin (CFL1), and Actin alpha cardiac muscle 1 (ACTC1) detection in aged cells, these proteins being involved in actin-filament polymerization and sharing co-activity in cell motility. Our present data reinforce knowledge about an age-related alteration in the synthesis of major proteins linked to the migratory and contractile functions of dermal human fibroblasts.
真皮成纤维细胞对于皮肤的稳态至关重要，其可协调细胞外基质成分的合成和降解。随着年龄的增长，真皮成纤维细胞中细胞外基质成分（如胶原蛋白和酶）的表达发生改变，导致皮肤机械张力降低和皮肤伤口愈合缺陷。本研究旨在通过 HLPC/MS 比较年轻（<35 岁）和老年（>55 岁）供体皮肤来源的成纤维细胞在静息或 TGF 刺激条件下的分泌组和蛋白质组特征，更好地了解成纤维细胞在衰老过程中经历的分子改变。比较年轻和老年成纤维细胞的分泌组，发现 16 种在静息状态下的蛋白和 11 种在 TGF-β1 处理 24 小时后的蛋白在两组细胞之间的表达方式有显著差异（倍数变化>2，<0.05），老年细胞分泌的蛋白数量减少了 77%。年轻和老年成纤维细胞的蛋白质组比较，在静息状态下有 63 种蛋白和在 TGF-β1 刺激条件下有 73 种蛋白发生显著变化，老年成纤维细胞中蛋白数量增加了 67%。差异表达的分子大多数属于细胞骨架相关蛋白，衰老的特征是成纤维细胞中 Coronin 1C（CORO1C）和 Filamin B（FLNB）的表达增加，而 Cofilin（CFL1）和 Actin alpha cardiac muscle 1（ACTC1）的检测减少，这些蛋白参与肌动蛋白丝聚合，在细胞运动中具有共同活性。我们目前的数据强化了关于与真皮人类成纤维细胞迁移和收缩功能相关的主要蛋白质的合成在年龄相关性改变的知识。
