BIOCHEMICAL-COMPOSITION OF THE CONNECTIVE-TISSUE IN KELOIDS AND ANALYSIS OF COLLAGEN-METABOLISM IN KELOID FIBROBLAST-CULTURES
BIOCHEMICAL-COMPOSITION OF THE CONNECTIVE-TISSUE IN KELOIDS AND ANALYSIS OF COLLAGEN-METABOLISM IN KELOID FIBROBLAST-CULTURES
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DOI：
10.1111/1523-1747.ep12265471
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发表时间：
1985-01-01
影响因子：
6.5
通讯作者：
UITTO, J
中科院分区：
文献类型：
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作者：
ABERGEL, RP;PIZZURRO, D;UITTO, J
疤痕疙瘩的组织学特征是结缔组织细胞外基质丰富。检查了疤痕疙瘩的结缔组织成分，并利用从疤痕疙瘩组织建立的成纤维细胞培养物分析了胶原代谢的细节。定量结缔组织分析表明胶原蛋白是疤痕疙瘩中主要的细胞外基质成分。与正常人类皮肤相比，遗传上不同的 I/III 型胶原蛋白的比例显着增加。通过放射性羟脯氨酸的形成来测量成纤维细胞培养物中的胶原生物合成：所研究的 9 个瘢痕疙瘩细胞培养物中的 5 个显示，与年龄、性别和传代匹配的对照皮肤成纤维细胞系相比，前胶原产量增加，而其余 4 个细胞系在对照范围内。瘢痕疙瘩成纤维细胞培养物是高胶原蛋白生产者，也表现出脯氨酰羟化酶活性升高。首先通过利用与前α2(I)链特异性c[互补]DNA的点印迹杂交测定I型前胶原特异性mRNA的丰度来检查成纤维细胞培养物中前胶原产量增加的机制。 4 个瘢痕疙瘩成纤维细胞系中 I 型原胶原 mRNA 水平显着增加，并且在相同培养物中 mRNA 水平与原胶原产生率之间存在良好的相关性。建议在转录水平上调节胶原蛋白基因表达。通过测定小分子量肽片段中的放射性羟脯氨酸来确定新合成的前胶原多肽的降解，从而检查成纤维细胞培养物中胶原代谢的分解代谢途径。在3个瘢痕疙瘩细胞培养物中，新合成的胶原蛋白多肽的降解低于正常对照的范围。新合成多肽降解的减少可能有助于某些瘢痕疙瘩成纤维细胞培养物中前胶原的积累。对于胶原蛋白在体内瘢痕疙瘩病变中的沉积，提出了两种可能的机制：第一，病变的生长可能是由于成纤维细胞局部失去对细胞外基质产生的控制所致；第二，新合成的原胶原多肽的降解减少可能有助于胶原蛋白在一些疤痕疙瘩中的沉积。
Keloids are histologically characterized by an abundance of the extracellular matrix of connective tissue. The connective tissue composition of keloids was examined, and the details of collagen metabolism analyzed utilizing fibroblast cultures established from keloid tissue. Quantitative connective tissue analyses indicated that collagen was the predominant extracellular matrix component in keloids. The ratio of genetically distinct collagens type I/III was significantly increased, as compared to normal human skin. Collagen biosynthesis was measured in fibroblast cultures by the formation of radioactive hydroxyproline: 5 of 9 keloid cell cultures studied demonstrated increased procollagen production in comparison to age-, sex- and passage-matched control skin fibroblast lines, while the remaining 4 cell lines were within the control range. Keloid fibroblast cultures which were high collagen producers also demonstrated elevated prolyl hydroxylase activity. The mechanisms of increased procollagen production in fibroblast cultures were first examined by assaying the abundance of type I procollagen-specific mRNA utilizing dot blot hybridizations with a pro.alpha.2(I)-chain-specific c[complementary]DNA. The type I procollagen mRNA levels were significantly increased in 4 keloid fibroblast lines, and a good correlation between the mRNA levels and the rate of procollagen production in the same cultures was noted. Regulation of the collagen gene expression on the transcriptional level is suggested. The catabolic pathway of collagen metabolism in fibroblast cultures was examined by determining the degradation of newly synthesized procollagen polypeptides through assay of radioactive hydroxyproline in small-MW peptide fragments. In 3 keloid cell cultures, the degradation of newly synthesized collagen polypeptides was below the range of normal controls. A reduced degradation of newly synthesized polypeptides might contribute to the accumulation of procollagen in some keloid fibroblast cultures. Two possible mechanisms are suggested for deposition of collagen in keloid lesions in vivo: 1st, the growth of the lesions may result from a localized loss of control of the extracellular matrix production by fibroblasts; 2nd, reduced degradation of the newly synthesized procollagen polypeptides may contribute to collagen deposition in some keloids.