Yudintceva Natalia M, Kolesnichenko Yulia V, Shatrova Alla N, Aksenov Nikolay D, Yartseva Natalia M, Shevtsov Maxim A, Fedorov Viacheslav S, Khotin Mikhail G, Ziganshin Rustam H, Mikhailova Natalia A
Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint-Petersburg, Russia.
School of Medicine and Life Sciences, Far Eastern Federal University, Campus 10 Ajax Bay, Russky Island, 690922 Vladivostok, Russia.
Biomedicines. 2024 Oct 10;12(10):2295. doi: 10.3390/biomedicines12102295.
Dermal fibroblasts (DFs) are key participants in skin hypertrophic scarring, and their properties are being studied to identify the molecular and cellular mechanisms underlying the pathogenesis of skin scarring. In the present work, we performed a comparative analysis of DFs isolated from normal skin (normal dermal fibroblasts, NDFs), and hypertrophic scar skin (hypertrophic scar fibroblasts, HTSFs). The fibroblasts were karyotyped and phenotyped, and experiments on growth rate, wound healing, and single-cell motility were conducted. Comparative analysis revealed a minor karyotype difference between cells. However, HTSFs are characterized by higher proliferation level and motility compared to NDFs. These significant differences may be associated with quantitative and qualitative differences in the cell secretome. A proteomic comparison of NDF and HTSF found that differences were associated with metabolic proteins reflecting physiological differences between the two cells lines. Numerous unique proteins were found only in the vesicular phase of vHTSFs. Some proteins involved in cell proliferation (protein-glutamine gamma-glutamyltransferase K) and cell motility (catenin delta-1), which regulate gene transcription and the activity of Rho family GTPases and downstream cytoskeletal dynamics, were identified. A number of proteins which potentially play a role in fibrosis and inflammation (mucin-5B, CD97, adhesion G protein-coupled receptor E2, antileukoproteinase, protein S100-A8 and S100-A9, protein caspase recruitment domain-containing protein 14) were detected in vHTSFs. A comparative analysis of primary cell cultures revealed their various properties, especially in the cell secretome. These proteins may be considered promising target molecules for developing treatment or prevention strategies for pathological skin scarring.
真皮成纤维细胞（DFs）是皮肤肥厚性瘢痕形成的关键参与者，目前正在对其特性进行研究，以确定皮肤瘢痕形成发病机制的分子和细胞机制。在本研究中，我们对从正常皮肤分离的真皮成纤维细胞（正常真皮成纤维细胞，NDFs）和肥厚性瘢痕皮肤分离的真皮成纤维细胞（肥厚性瘢痕成纤维细胞，HTSFs）进行了比较分析。对成纤维细胞进行了核型分析和表型分析，并进行了生长速率、伤口愈合和单细胞运动性实验。比较分析显示细胞之间存在微小的核型差异。然而，与NDFs相比，HTSFs具有更高的增殖水平和运动性。这些显著差异可能与细胞分泌组的数量和质量差异有关。对NDF和HTSF的蛋白质组学比较发现，差异与反映这两种细胞系生理差异的代谢蛋白有关。仅在vHTSFs的囊泡期发现了许多独特的蛋白质。鉴定出了一些参与细胞增殖（蛋白质-谷氨酰胺γ-谷氨酰转移酶K）和细胞运动（连环蛋白δ-1）的蛋白质，它们调节基因转录以及Rho家族GTP酶的活性和下游细胞骨架动力学。在vHTSFs中检测到了一些可能在纤维化和炎症中起作用的蛋白质（粘蛋白-5B、CD97、粘附G蛋白偶联受体E2、抗白细胞蛋白酶、蛋白质S100-A8和S100-A9、含半胱天冬酶募集结构域的蛋白质14）。对原代细胞培养物的比较分析揭示了它们的各种特性，尤其是在细胞分泌组方面。这些蛋白质可能被认为是开发病理性皮肤瘢痕治疗或预防策略的有前景的靶标分子。
