Venous ulcer fibroblasts compared with normal fibroblasts show differences in collagen but not fibronectin production under both normal and hypoxic conditions
Venous ulcer fibroblasts compared with normal fibroblasts show differences in collagen but not fibronectin production under both normal and hypoxic conditions
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DOI：
10.1111/1523-1747.ep12329920
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发表时间：
1996-01-01
影响因子：
6.5
通讯作者：
Ferguson, MWJ
中科院分区：
文献类型：
--
作者：
Herrick, SE;Ireland, GW;Ferguson, MWJ
先前的免疫细胞化学分析显示，与周围的“正常”真皮相比，静脉溃疡的基底缺乏纤维连接蛋白。在此，我们研究溃疡成纤维细胞的合成能力受损是否可以作为这一观察的基础。将在慢性静脉性腿部溃疡边缘活检组织中培养的溃疡成纤维细胞与从部位和年龄匹配的正常皮肤活检组织中生长的正常成纤维细胞进行比较，以确定它们合成基质分子的能力。胶原酶敏感性计数和明胶亲和力计数，正常成纤维细胞比溃疡成纤维细胞产生更多的胶原，当细胞培养在塑料和胶原凝胶。然而，在纤连蛋白合成中，两种细胞类型在任一基质上没有重大差异，溃疡成纤维细胞暴露的缺氧环境可能导致两种成纤维细胞类型在胶原合成中的内在差异。当我们测试缺氧条件下培养细胞的效果，这两种细胞类型产生较少的胶原蛋白，特别是正常的成纤维细胞生长在胶原蛋白凝胶，但没有缺氧对fibronectin合成的影响。我们得出结论，静脉溃疡边缘衍生的成纤维细胞有受损的能力，在体外合成胶原蛋白，但正常合成纤连蛋白。因此，静脉溃疡中发现的低水平纤连蛋白不太可能是由于溃疡细胞不能产生它或对缺氧条件的反应，而可能是由于这些溃疡中存在的蛋白酶降解合成的纤连蛋白。
Previous immunocytochemical analysis showed that the base of venous ulcers was deficient in fibronectin compared with surrounding ''normal'' dermis. Here, we investigate whether impaired synthetic ability of ulcer fibroblasts could underlie this observation, Ulcer fibroblasts, established in culture from biopsies of the edge of chronic venous leg ulcers, were compared with normal fibroblasts grown from biopsies of site- and age-matched normal skin for their ability to synthesize matrix molecules, Collagen and fibronectin synthesis were measured following metabolic labeling, as collagenase susceptible counts and counts with gelatin affinity, respectively.More collagen was produced by normal fibroblasts than ulcer fibroblasts, both when the cells were cultured on plastic and in collagen gels. In fibronectin synthesis, however, there was no major difference between the two cell types on either substratum, The hypoxic environment to which ulcer fibroblasts are exposed may have caused the intrinsic differences in collagen synthesis by the two fibroblast types. When we tested the effect of culturing cells under hypoxic conditions, both cell types produced less collagen, especially normal fibroblasts grown in a collagen gel, but there was no effect of hypoxia on fibronectin synthesis.We conclude that venous ulcer edge-derived fibroblasts have an impaired ability to synthesize collagen in vitro, but synthesize fibronectin normally. Therefore, the low level of fibronectin found in venous ulcers is not likely to be due to the inability of ulcer cells to produce it or to the response to hypoxic conditions but may be due to the degradation of synthesized fibronectin by proteases present in these ulcers.