Boelsma E, Pavel S, Ponec M
Department of Dermatology, University Hospital Leiden, The Netherlands.
Dermatology. 1995;191(3):226-33. doi: 10.1159/000246550.
Scleroderma is a fibrotic disorder of unknown etiology that is characterized by excessive collagen synthesis and its deposition in the skin and various internal organs.
To examine whether an overproduction of extracellular matrix molecules is a result of either increased fibroblast proliferation or increased collagen synthesis. As results of clinical trials with 1,25-dihydroxyvitamin D3 (calcitriol) have suggested beneficial effect in the treatment of scleroderma patients, the effects of calcitriol on fibroblasts derived from scleroderma and normal skin has been examined as well.
Cultures of fibroblasts were established from biopsies from involved and uninvolved skin of scleroderma patients and from skin of healthy subjects, and compared with respect to proliferation, collagen synthesis and collagen lattice contraction.
No significant differences in cell proliferation and in the extent of fibroblast-induced collagen lattice contraction have been found between scleroderma patients exhibited a disorganized growth pattern in a monolayer culture in contrast to normal fibroblasts. Collagen synthesis tends to be higher in scleroderma fibroblasts as compared with controls. Calcitriol exerted an antiproliferative and antisynthetic effect on fibroblasts, which, however, did not discriminate healthy fibroblasts from fibroblasts derived from involved or uninvolved scleroderma plaques.
Our findings suggest that collagen accumulation may not result from increased proliferation or altered dynamic properties of fibroblasts in a scleroderma lesion but from increased collagen biosynthesis. We additionally found that calcitriol does not selectively affect scleroderma fibroblasts.
硬皮病是一种病因不明的纤维化疾病，其特征是胶原蛋白过度合成并沉积于皮肤和各种内脏器官。
研究细胞外基质分子的过度产生是否是成纤维细胞增殖增加或胶原蛋白合成增加的结果。由于1,25 - 二羟维生素D3（骨化三醇）的临床试验结果表明其对硬皮病患者的治疗有有益作用，因此也研究了骨化三醇对硬皮病皮肤和正常皮肤来源的成纤维细胞的影响。
从硬皮病患者受累和未受累皮肤的活检组织以及健康受试者的皮肤中建立成纤维细胞培养物，并比较其增殖、胶原蛋白合成和胶原晶格收缩情况。
在硬皮病患者与正常成纤维细胞相比，单层培养中呈现无序生长模式的硬皮病患者之间，在细胞增殖和成纤维细胞诱导的胶原晶格收缩程度上未发现显著差异。与对照组相比，硬皮病成纤维细胞中的胶原蛋白合成倾向于更高。骨化三醇对成纤维细胞具有抗增殖和抗合成作用，然而，它并不能区分健康成纤维细胞与来自硬皮病受累或未受累斑块的成纤维细胞。
我们的研究结果表明，硬皮病病变中胶原蛋白的积累可能不是由于成纤维细胞增殖增加或其动态特性改变，而是由于胶原蛋白生物合成增加。我们还发现骨化三醇不会选择性地影响硬皮病成纤维细胞。
