Takehara K, Soma Y, Igarashi A, Kikuchi K, Moro A, Ishibashi Y
Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan.
Arch Dermatol Res. 1991;283(7):461-4. doi: 10.1007/BF00371783.
Abnormal growth regulation in lesional skin fibroblasts may be related to scleroderma pathogenesis. We report on the abnormal response of cultured fibroblasts derived from sclerotic lesions to various growth factors. We investigated the responses of skin fibroblasts (10 strains) and normal fibroblasts (9 strains) to the growth factors as PDGF, TGF-beta 1, EGF and basic FGF. Experiments were conducted during the proliferation and confluent stages. PDGF, EGF and basic FGF stimulated fibroblast growth during the proliferation and confluent stages, but the response of scleroderma fibroblasts was significantly lower than that of normal fibroblasts. TGF-beta 1 slightly stimulated confluent fibroblast growth and inhibited proliferating fibroblasts, and the response of scleroderma fibroblasts exceeded that of normal fibroblasts. The decreased response to growth-stimulating factors observed in scleroderma fibroblasts suggests that cultured fibroblasts derived from scleroderma lesions were already senescent because they have been activated by growth-stimulating factors and repeatedly divided in vivo. Thus, abnormal growth regulation of skin fibroblasts may be partially related to the pathogenesis of scleroderma.
病变皮肤成纤维细胞的生长调节异常可能与硬皮病的发病机制有关。我们报道了源自硬化性病变的培养成纤维细胞对各种生长因子的异常反应。我们研究了皮肤成纤维细胞（10株）和正常成纤维细胞（9株）对血小板衍生生长因子（PDGF）、转化生长因子β1（TGF-β1）、表皮生长因子（EGF）和碱性成纤维细胞生长因子（bFGF）等生长因子的反应。实验在增殖期和汇合期进行。PDGF、EGF和bFGF在增殖期和汇合期均刺激成纤维细胞生长，但硬皮病成纤维细胞的反应明显低于正常成纤维细胞。TGF-β1轻微刺激汇合的成纤维细胞生长并抑制增殖的成纤维细胞，且硬皮病成纤维细胞的反应超过正常成纤维细胞。在硬皮病成纤维细胞中观察到的对生长刺激因子反应的降低表明，源自硬皮病病变的培养成纤维细胞已经衰老，因为它们已被生长刺激因子激活并在体内反复分裂。因此，皮肤成纤维细胞的生长调节异常可能部分与硬皮病的发病机制有关。
