Mauch C, Kozlowska E, Eckes B, Krieg T
Department of Dermatology, University of Cologne, Köln, FRG.
Exp Dermatol. 1992 Nov;1(4):185-90. doi: 10.1111/j.1600-0625.1992.tb00187.x.
In systemic scleroderma (SSc) excessive deposition of collagen leads to fibrosis of various tissues including the skin. Previous studies have demonstrated that scleroderma fibroblasts in explant monolayer cultures are heterogeneous with respect to their levels of collagen synthesis. The critical role played by the extracellular matrix (ECM) in the modulation of fibroblast metabolism prompted us to study the regulation of collagen synthesis in scleroderma fibroblasts grown within three-dimensional collagen gels, a culture system representing more physiological conditions than monolayer cultures. Normal fibroblasts grown in this system dramatically reduce their collagen synthesis as compared to monolayer cultures. Quantification of total protein and collagen synthesis showed that scleroderma fibroblasts did not demonstrate the down regulation of collagen synthesis as observed in control fibroblasts, resulting in a much higher collagen synthesis in scleroderma fibroblasts compared to controls. However, also in this system scleroderma fibroblasts were heterogeneous in their response to the collagenous lattice. Ten strains were investigated, of which 3 were indistinguishable from controls, while 7 maintained higher levels of collagen production. In addition, our data showed that the changes in collagen synthesis on the protein level were accompanied by respective up- or downregulation on the mRNA level. These results indicate that an altered response to the surrounding ECM is an important factor in the disturbed regulation of connective tissue synthesis in scleroderma fibroblasts observed in vivo.
在系统性硬化症（SSc）中，胶原蛋白的过度沉积会导致包括皮肤在内的各种组织发生纤维化。先前的研究表明，在外植体单层培养中的硬皮病成纤维细胞在胶原蛋白合成水平方面具有异质性。细胞外基质（ECM）在调节成纤维细胞代谢中所起的关键作用促使我们研究在三维胶原蛋白凝胶中生长的硬皮病成纤维细胞中胶原蛋白合成的调控，三维胶原蛋白凝胶培养系统比单层培养更能代表生理条件。与单层培养相比，在此系统中生长的正常成纤维细胞显著降低其胶原蛋白合成。总蛋白和胶原蛋白合成的定量分析表明，硬皮病成纤维细胞并未表现出如对照成纤维细胞中所观察到的胶原蛋白合成下调，导致硬皮病成纤维细胞中的胶原蛋白合成比对照高得多。然而，在这个系统中，硬皮病成纤维细胞对胶原晶格的反应也存在异质性。研究了10个菌株，其中3个与对照无差异，而7个保持较高水平的胶原蛋白产生。此外，我们的数据表明，蛋白质水平上胶原蛋白合成的变化伴随着mRNA水平上相应的上调或下调。这些结果表明，对周围ECM的反应改变是体内观察到的硬皮病成纤维细胞结缔组织合成调节紊乱的一个重要因素。
