Jimenez S A, Feldman G, Bashey R I, Bienkowski R, Rosenbloom J
Biochem J. 1986 Aug 1;237(3):837-43. doi: 10.1042/bj2370837.
Progressive systemic sclerosis (PSS), is a connective tissue disease characterized by excessive accumulation of collagen in the skin and various internal organs which is due, at least in part, to increased collagen production by PSS fibroblasts. In order to examine the molecular mechanisms responsible for this abnormality, we compared the kinetics of collagen biosynthesis, the intracellular degradation of collagen and the expression of Types I and III procollagen genes between normal and PSS dermal fibroblasts in culture. Two age- and sex-matched normal and PSS dermal fibroblast cell lines were studied. The results showed that the PSS cultures produced higher amounts of collagen than did normal fibroblasts and displayed an abnormal kinetic pattern. Furthermore, the PSS cells showed a slight but statistically significant increase in the fraction of collagen degraded intracellularly when compared with normal cells (23% against 18% respectively). The levels of mRNA for procollagen Types I and III were determined by Northern and dot-blot hybridization with specific cloned cDNA probes for alpha 1(I), alpha 2(I) and alpha 1(III) and it was found that they were 2-3-fold higher for each of the three chains in the PSS cell lines compared with the controls. These findings indicate, therefore, that the overproduction of collagen characteristic of PSS fibroblasts can be largely accounted for by the increased levels of collagen mRNA.
进行性系统性硬化症（PSS）是一种结缔组织疾病，其特征是皮肤和各种内脏器官中胶原蛋白过度积累，这至少部分归因于PSS成纤维细胞胶原蛋白生成增加。为了研究导致这种异常的分子机制，我们比较了培养的正常和PSS真皮成纤维细胞之间胶原蛋白生物合成的动力学、胶原蛋白的细胞内降解以及I型和III型前胶原基因的表达。研究了两个年龄和性别匹配的正常和PSS真皮成纤维细胞系。结果表明，PSS培养物产生的胶原蛋白比正常成纤维细胞多，并且显示出异常的动力学模式。此外，与正常细胞相比，PSS细胞细胞内降解的胶原蛋白比例略有增加，但具有统计学意义（分别为23%对18%）。用针对α1（I）、α2（I）和α1（III）的特异性克隆cDNA探针通过Northern和斑点印迹杂交法测定I型和III型前胶原的mRNA水平，发现PSS细胞系中三条链各自的mRNA水平比对照高2至3倍。因此，这些发现表明，PSS成纤维细胞胶原蛋白过度产生的特征很大程度上可以由胶原蛋白mRNA水平的增加来解释。
