Dataset Information

Platelet-Released Growth Factors Induce Genes Involved in Extracellular Matrix Formation in Human Fibroblasts.

ABSTRACT: 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.

SUBMITTER: Bayer A

PROVIDER: S-EPMC8508971 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Platelet-Released Growth Factors Induce Genes Involved in Extracellular Matrix Formation in Human Fibroblasts.

Bayer Andreas A Wijaya Bernard B Rademacher Franziska F Möbus Lena L Preuß Mark M Singh Michael M Tohidnezhad Mersedeh M Kubo Yusuke Y Rodewald Meno M Behrendt Peter P Weitkamp Jan-Tobias JT Gläser Regine R Harder Jürgen J

International journal of molecular sciences 20210929 19

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 (G ...[more]

PMID: 34638874

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Project description:One of the most potent pro-fibrotic cytokines is transforming growth factor (TGF?). TGF? is involved in the activation of fibroblasts into myofibroblasts, resulting in the hallmark of fibrosis: the pathological accumulation of collagen. Interleukin-1? (IL1?) can influence the severity of fibrosis, however much less is known about the direct effects on fibroblasts. Using lung and dermal fibroblasts, we have investigated the effects of IL1?, TGF?1, and IL1? in combination with TGF?1 on myofibroblast formation, collagen synthesis and collagen modification (including prolyl hydroxylase, lysyl hydroxylase and lysyl oxidase), and matrix metalloproteinases (MMPs). We found that IL1? alone has no obvious pro-fibrotic effect on fibroblasts. However, IL1? is able to inhibit the TGF?1-induced myofibroblast formation as well as collagen synthesis. Glioma-associated oncogene homolog 1 (GLI1), the Hedgehog transcription factor that is involved in the transformation of fibroblasts into myofibroblasts is upregulated by TGF?1. The addition of IL1? reduced the expression of GLI1 and thereby also indirectly inhibits myofibroblast formation. Other potentially anti-fibrotic effects of IL1? that were observed are the increased levels of MMP1, -2, -9 and -14 produced by fibroblasts exposed to TGF?1/IL1? in comparison with fibroblasts exposed to TGF?1 alone. In addition, IL1? decreased the TGF?1-induced upregulation of lysyl oxidase, an enzyme involved in collagen cross-linking. Furthermore, we found that lung and dermal fibroblasts do not always behave identically towards IL1?. Suppression of COL1A1 by IL1? in the presence of TGF?1 is more pronounced in lung fibroblasts compared to dermal fibroblasts, whereas a higher upregulation of MMP1 is seen in dermal fibroblasts. The role of IL1? in fibrosis should be reconsidered, and the differences in phenotypical properties of fibroblasts derived from different organs should be taken into account in future anti-fibrotic treatment regimes.

Project description:The dermis of human skin contains large numbers of fibroblasts that are responsible for the production of the extracellular matrix (ECM) that supporting skin integrity, elasticity and wound healing. Previously, an in vivo study demonstrated that dermal fibroblasts siting in the lower dermis are capable to convert into skin adipose layer and hence fibroblast lipogenesis may vary the structure and elasticity of dermis. In the present study, Hs68 human dermal fibroblasts were utilized as an in vitro model to study the lipogenesis via using adipogenic differentiation medium (ADM). Baicalein, isolated from Scutellaria baicalensis, is one of the flavonoids to inhibit adipocyte differentiation due to high antioxidant activity in vitro. In order to develop a suitable formulation for baicalein (a poorly water-soluble drug), soybean phosphatidylcholine (SPC) was used to prepare baicalein-loaded liposomes to enhance drug bioavailability. Our results demonstrated that liposome-encapsulated baicalein protected cell viability and increased cellular uptake efficiency of Hs68 fibroblasts. Lipid accumulation, triglyceride synthesis and gene expressions of lipogenesis enzymes (FABP4 and LPL) were significantly increased in ADM-stimulated Hs68 fibroblasts but subsequently suppressed by liposome-encapsulated baicalein. In addition, ADM-induced TNF-α expression and related inflammatory factors was down-regulated by liposome-encapsulated baicalein. Through ADM-induced lipogenesis, the protein expression of elastin, type I and type III collagens increased remarkably, whereas liposome-encapsulated baicalein can down-regulate ADM-induced ECM protein synthesis. Taken together, we found that liposome-encapsulated baicalein can inhibit ADM-induced lipid accumulation and ECM formation in Hs68 fibroblasts through the suppression of lipogenesis enzymes and inflammatory responses. Liposome-encapsulated baicalein may have the potential to improve wound healing and restore skin structure after skin injury.

Dataset Information

Platelet-Released Growth Factors Induce Genes Involved in Extracellular Matrix Formation in Human Fibroblasts.

Publications

Platelet-Released Growth Factors Induce Genes Involved in Extracellular Matrix Formation in Human Fibroblasts.

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