Zurita-Salinas Camilo S, Krötzsch Edgar, Díaz de León Lino, Alcocer-Varela Jorge
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan, 14000, Mexico City, Mexico.
Rheumatol Int. 2004 Sep;24(5):283-90. doi: 10.1007/s00296-003-0364-6. Epub 2003 Nov 5.
To investigate collagen turnover and proliferation in dermal fibroblasts from patients with systemic sclerosis (SSc) and their relationship with disease duration and cellular subpopulations, SSc patients were grouped by disease duration (less than 2.5 years or more than 7 years). Control and SSc fibroblasts were obtained from skin biopsies. Collagen biosynthesis was determined by [14C]-proline uptake. Type I/III collagens, gelatinolytic activity, and tissue inhibitors of metalloproteinases (TIMP)-1 and -2 were evaluated by electrophoresis, zymography, and enzyme-linked immunosorbent assay, respectively. Total collagen synthesis and the levels of alpha1(I), alpha2(I), and alpha1(III) chains, as well as TIMP-1 and proliferation were increased in fibroblasts only from patients with early-stage SSc. Gelatinolytic activity did not vary among the groups. This metabolic condition favors a higher local fibroblast population and is characterized by a heterogeneous clonal response in which the majority exhibited higher levels of collagen and TIMP-1 synthesis as well as an increase in their proliferation patterns involving hyper-reactive fibroblast subsets.
为了研究系统性硬化症（SSc）患者真皮成纤维细胞中的胶原蛋白周转和增殖情况，以及它们与疾病持续时间和细胞亚群的关系，将SSc患者按疾病持续时间（小于2.5年或大于7年）分组。对照和成纤维细胞取自皮肤活检组织。通过[14C] - 脯氨酸摄取测定胶原蛋白生物合成。分别通过电泳、酶谱分析和酶联免疫吸附测定评估I/III型胶原蛋白、明胶酶活性以及金属蛋白酶组织抑制剂（TIMP）-1和-2。仅早期SSc患者的成纤维细胞中总胶原蛋白合成、α1（I）、α2（I）和α1（III）链水平以及TIMP-1和增殖水平增加。各组之间明胶酶活性没有差异。这种代谢状况有利于局部成纤维细胞数量增加，其特征是克隆反应异质性，其中大多数表现出较高水平的胶原蛋白和TIMP-1合成以及其增殖模式增加，涉及高反应性成纤维细胞亚群。
