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Serum stimulation cell-cell interactions and extracellular matrix independently influence smooth muscle cell phenotype in vitro.

机译:血清刺激细胞间相互作用和细胞外基质在体外独立影响平滑肌细胞表型。

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摘要

Vascular injury profoundly alters the vessel wall microenvironment, and smooth muscle cells respond with cell cycle re-entry, loss of contractile elements, extracellular matrix remodeling, and altered signaling by endogenous growth factors and their receptors. Environmental cues include stimulation by exogenous mitogens and both cell-cell and cell-matrix interactions. Modeling this process in smooth muscle cells in vitro, these environmental determinants were varied independently and the phenotypic consequences assessed. Mitogenic stimulation with serum promoted the synthesis of collagen and fibronectin and the expression of fibroblast growth factor receptor-1 and suppressed the content of smooth muscle alpha-actin, myosin heavy chain, and basic fibroblast growth factor. Low cell density (reduced cell-cell contact) was also associated with enhanced extracellular matrix protein production, increased fibroblast growth factor receptor-1 expression, and reduced contractile protein and basic fibroblast growth factor content. The influence of serum stimulation and reduced cell-cell contact were independent and additive. Provision of a type I collagen matrix blunted the influence of serum and cell-cell contact on collagen synthesis but had minor effects on other measures of phenotype. Environmental factors thus independently influence smooth muscle cell phenotype, including endogenous growth factor expression and responsiveness, which can in turn influence the microenvironment of the vessel wall after injury.
机译:血管损伤深刻地改变了血管壁的微环境,平滑肌细胞通过细胞周期的再进入,收缩元件的丢失,细胞外基质的重塑以及内源性生长因子及其受体的信号改变而做出反应。环境提示包括外源促分裂原的刺激以及细胞与细胞和细胞与基质的相互作用。在体外平滑肌细胞中对该过程进行建模时,这些环境决定因素是独立变化的,并且评估了表型后果。血清促成丝刺激促进胶原蛋白和纤连蛋白的合成以及成纤维细胞生长因子受体-1的表达,并抑制平滑肌α-肌动蛋白,肌球蛋白重链和碱性成纤维细胞生长因子的含量。低细胞密度(减少的细胞间接触)也与细胞外基质蛋白产生增加,成纤维细胞生长因子受体1表达增加,收缩蛋白和碱性成纤维细胞生长因子含量降低有关。血清刺激和减少细胞-细胞接触的影响是独立的和累加的。 I型胶原蛋白基质的提供减弱了血清和细胞间接触对胶原蛋白合成的影响,但对其他表型指标影响较小。因此,环境因素独立地影响平滑肌细胞的表型,包括内源性生长因子的表达和响应性,这反过来又可以影响损伤后血管壁的微环境。

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