Friedman D W, Boyd C D, Mackenzie J W, Norton P, Olson R M, Deak S B
Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08903.
J Surg Res. 1993 Aug;55(2):214-22. doi: 10.1006/jsre.1993.1132.
The synthesis of type I and III collagens in cultured skin fibroblasts from normal skin, normal scar, hypertrophic scar, and keloids was examined. The ratio of type I/III collagen was significantly elevated in keloids compared to that in the other groups. When mRNA steady-state levels coding for alpha 1(I) procollagen were determined, it was apparent that this increase in the type I/III collagen ratio in keloids was paralleled by a specific increase in alpha 1(I) procollagen mRNA. This specific increase in alpha 1(I) procollagen mRNA in keloids was the result of increased gene expression because the transcription rate of the alpha 1(I) procollagen gene was significantly elevated in keloids, as determined by nuclear runoff transcription. The rate of transcription of the alpha 1(I) procollagen gene was also elevated in hypertrophic scars, although no concomitant increase in alpha 1(I) procollagen mRNA levels or alteration in the type I/III collagen ratio was observed. These data indicate that the rate of gene transcription of alpha 1(I) procollagen is increased in both hypertrophic scars and keloids, but only keloids exhibit increased steady-state levels of alpha 1(I) procollagen mRNA and concurrent increases in type I collagen. These results suggest that at least two distinct mechanisms, one pretranscriptional and one post-transcriptional, regulate type I collagen synthesis. It is possible, therefore, that in keloids, neither mechanism functions efficiently to down-regulate type I collagen. In hypertrophic scars, however, the post-transcriptional mechanisms are able to decrease elevated levels of mRNA coding for alpha 1(I) procollagen that result from increased transcription of the alpha 1(I) procollagen gene.
研究了来自正常皮肤、正常瘢痕、增生性瘢痕和瘢痕疙瘩的培养皮肤成纤维细胞中I型和III型胶原蛋白的合成情况。与其他组相比，瘢痕疙瘩中I型/III型胶原蛋白的比例显著升高。当测定编码α1(I)前胶原的mRNA稳态水平时，很明显瘢痕疙瘩中I型/III型胶原蛋白比例的增加与α1(I)前胶原mRNA的特异性增加平行。瘢痕疙瘩中α1(I)前胶原mRNA的这种特异性增加是基因表达增加的结果，因为通过核转录分析确定，瘢痕疙瘩中α1(I)前胶原基因的转录率显著升高。增生性瘢痕中α1(I)前胶原基因的转录率也升高，尽管未观察到α1(I)前胶原mRNA水平的相应增加或I型/III型胶原蛋白比例的改变。这些数据表明，增生性瘢痕和瘢痕疙瘩中α1(I)前胶原的基因转录率均增加，但只有瘢痕疙瘩表现出α1(I)前胶原mRNA稳态水平的增加以及I型胶原蛋白的同时增加。这些结果表明，至少有两种不同的机制，一种是转录前机制，一种是转录后机制，调节I型胶原蛋白的合成。因此，在瘢痕疙瘩中，这两种机制可能都不能有效地下调I型胶原蛋白合成。然而，在增生性瘢痕中，转录后机制能够降低因α1(I)前胶原基因转录增加而导致的编码α1(I)前胶原的mRNA升高水平。
