Kähäri V M, Häkkinen L, Westermarck J, Larjava H
Department of Dermatology, University of Turku, Finland.
J Invest Dermatol. 1995 Apr;104(4):503-8. doi: 10.1111/1523-1747.ep12605969.
Proteoglycans participate in the assembly of extracellular matrix, directly by interacting with other matrix components and indirectly by regulating cellular growth-factor responses. We have studied the regulation of gene expression of two small extracellular matrix chondroitin/dermatan sulfate proteoglycans, decorin and biglycan, by dexamethasone and retinoic acid in cultured human skin fibroblasts. Dexamethasone increased decorin production, maximally 4.8-fold, and decorin mRNA levels up to 2.3-fold, but had no effect on biglycan production or mRNA levels. Dexamethasone also prevented transforming growth factor-beta-elicited down-regulation of decorin mRNA levels and production by dermal fibroblasts. In addition, dexamethasone potently inhibited enhancement of biglycan production and mRNA levels by transforming growth factor-beta. Retinoic acid dose dependently reduced decorin mRNA levels (by 51%) and production (by 72%), but had no effect on biglycan gene expression. Retinoic acid did not alter the effect of transforming growth factor-beta on decorin or biglycan production or mRNA levels. These results provide evidence that the effects of glucocorticoids and retinoids on dermal connective tissue are partially mediated via altered expression of decorin and biglycan, which both in turn regulate the activity of transforming growth factor-beta, the most potent stimulator of connective tissue deposition.
蛋白聚糖通过与其他基质成分直接相互作用以及通过调节细胞生长因子反应间接参与细胞外基质的组装。我们研究了地塞米松和视黄酸对培养的人皮肤成纤维细胞中两种小细胞外基质软骨素/硫酸皮肤素蛋白聚糖（核心蛋白聚糖和双糖链蛋白聚糖）基因表达的调节作用。地塞米松增加了核心蛋白聚糖的产生，最大增加4.8倍，核心蛋白聚糖mRNA水平提高了2.3倍，但对双糖链蛋白聚糖的产生或mRNA水平没有影响。地塞米松还阻止了转化生长因子-β引起的真皮成纤维细胞中核心蛋白聚糖mRNA水平和产生的下调。此外，地塞米松强烈抑制转化生长因子-β对双糖链蛋白聚糖产生和mRNA水平的增强作用。视黄酸剂量依赖性地降低了核心蛋白聚糖mRNA水平（降低51%）和产生（降低72%），但对双糖链蛋白聚糖基因表达没有影响。视黄酸没有改变转化生长因子-β对核心蛋白聚糖或双糖链蛋白聚糖产生或mRNA水平的影响。这些结果提供了证据，表明糖皮质激素和类维生素A对真皮结缔组织的作用部分是通过核心蛋白聚糖和双糖链蛋白聚糖表达的改变介导的，而这两者又反过来调节转化生长因子-β的活性，转化生长因子-β是结缔组织沉积最有效的刺激因子。
