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血小板衍生生长因子诱导人成纤维细胞中细胞外基质形成相关基因。

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

机构信息

Institute of Anatomy, Kiel University, 24098 Kiel, Germany.

Department of Dermatology, University Medical Center of Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.

出版信息

Int J Mol Sci. 2021 Sep 29;22(19):10536. doi: 10.3390/ijms221910536.

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.

摘要

血小板浓缩物产品由于其再生特性,在许多医学学科中越来越多地被使用。由于它们含有多种趋化因子、细胞因子和生长因子,因此被用于支持慢性或复杂伤口的愈合。迄今为止,其潜在的细胞机制尚未得到充分研究。因此,我们分析了血小板释放生长因子(PRGF)对人真皮成纤维细胞的影响。PRGF 处理的成纤维细胞的全转录组测序和基因本体(GO)富集分析显示,几种参与细胞外基质(ECM)形成的基因被诱导。PRGF 处理的成纤维细胞和皮肤外植体的实时 PCR 分析证实了 ECM 相关基因的诱导,特别是转化生长因子β诱导蛋白(TGFBI)、纤维连接蛋白 1(FN1)、基质金属蛋白酶 9(MMP-9)、转谷氨酰胺酶 2(TGM2)、铁蛋白家族成员 1(FERMT1)、胶原 I 型 α1(COL1A1)、解整合素金属蛋白酶 19(ADAM19)、丝氨酸蛋白酶抑制剂家族 E 成员 1(SERPINE1)和赖氨酰氧化酶样 3(LOXL3)。这些基因的诱导是时间依赖性的,部分受表皮生长因子受体(EGFR)的影响。此外,PRGF 还诱导成纤维细胞的迁移和增殖。综上所述,PRGF 对人成纤维细胞的观察到的作用可能有助于支持血小板浓缩物产品有益的伤口愈合作用的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f368/8508971/9f3eb7d12555/ijms-22-10536-g001.jpg

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