PT Journal AU Bayer, A Wijaya, B Rademacher, F Möbus, L Preuß, M Singh, M Tohidnezhad, M Kubo, Y Rodewald, M Behrendt, P Weitkamp, J Gläser, R Harder, J TI Platelet-Released Growth Factors Induce Genes Involved in Extracellular Matrix Formation in Human Fibroblasts SO International journal of molecular sciences PY 2021 VL 22 IS 19 PU MDPI AG DI 10.3390/ijms221910536 WP https://macau.uni-kiel.de/receive/macau_mods_00002671 LA en DE Blood Platelets; Cells, Cultured; Extracellular Matrix; Fibroblasts; Humans; Intercellular Signaling Peptides and Proteins; Extracellular Matrix Proteins; Cell Proliferation; Cell Movement; Collagen Type I, alpha 1 Chain; Extracellular matrix (ECM); Wound healing; Platelet-released Growth Factors (Prgf) SN 1661-6596 AB Platelet concentrate products are increasingly used in many medical disciplines due to their regenerative properties. As they contain a variety of chemokines, cytokines, and growth factors, they are used to support the healing of chronic or complicated wounds. To date, underlying cellular mechanisms have been insufficiently investigated. Therefore, we analyzed the influence of Platelet-Released Growth Factors (PRGF) on human dermal fibroblasts. Whole transcriptome sequencing and gene ontology (GO) enrichment analysis of PRGF-treated fibroblasts revealed an induction of several genes involved in the formation of the extracellular matrix (ECM). Real-time PCR analyses of PRGF-treated fibroblasts and skin explants confirmed the induction of ECM-related genes, in particular transforming growth factor beta-induced protein (TGFBI), fibronectin 1 (FN1), matrix metalloproteinase-9 (MMP-9), transglutaminase 2 (TGM2), fermitin family member 1 (FERMT1), collagen type I alpha 1 (COL1A1), a disintegrin and metalloproteinase 19 (ADAM19), serpin family E member 1 (SERPINE1) and lysyl oxidase-like 3 (LOXL3). The induction of these genes was time-dependent and in part influenced by the epidermal growth factor receptor (EGFR). Moreover, PRGF induced migration and proliferation of the fibroblasts. Taken together, the observed effects of PRGF on human fibroblasts may contribute to the underlying mechanisms that support the beneficial wound-healing effects of thrombocyte concentrate products. PI Basel ER