Autor: |
Yudintceva NM; Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint-Petersburg, Russia., Kolesnichenko YV; Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint-Petersburg, Russia., Shatrova AN; Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint-Petersburg, Russia., Aksenov ND; Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint-Petersburg, Russia., Yartseva NM; Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint-Petersburg, Russia., Shevtsov MA; 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., Fedorov VS; Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint-Petersburg, Russia., Khotin MG; Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint-Petersburg, Russia., Ziganshin RH; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, Miklukho-Maklaya Street 16/10, 117997 Moscow, Russia., Mikhailova NA; Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint-Petersburg, Russia. |
Abstrakt: |
Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. |