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烧伤后增生性瘢痕组织中胰岛素样生长因子-1 mRNA的表达增强及其在真皮成纤维细胞中的促纤维化作用

Enhanced expression of mRNA for insulin-like growth factor-1 in post-burn hypertrophic scar tissue and its fibrogenic role by dermal fibroblasts.

作者信息

Ghahary A, Shen Y J, Nedelec B, Scott P G, Tredget E E

机构信息

Department of Surgery, University of Alberta, Edmonton, Canada.

出版信息

Mol Cell Biochem. 1995 Jul 5;148(1):25-32. doi: 10.1007/BF00929499.

Abstract

Hypertrophic scarring (HSc) which frequently develops in patients following severe thermal injury is characterized by accumulation of extracellular matrix (ECM) proteins including type I and type III collagen. In this study, we examined the presence and quantity of IGF-1 mRNA transcripts in post-burn HSc. The results of dot blot experiments showed a 77.5% (100 +/- 8.15 vs 177.5 +/- 19, p < 0.01) increase in expression of IGF-1 IIIRNA in HSc tissue relative to normal dermis obtained from the same patients. A Northern blot analysis confirmed the specificity of the IGF-1 cDNA. This cDNA visualized four different transcripts with apparent sizes of 7.0, 3.9, 1.8 and 1.0 kb, similar to those previously reported. The possible fibrogenic role of IGF-1 was examined by analyzing the effect of this growth factor on the expression of mRNA for the pro alpha 1(I) chain of type I procollagen and the pro alpha 1(III) chain of type III procollagen in dermal fibroblasts. IGF-1 increased the expression of these transcripts as early as 6 h and the effect was maximal at 24 h. Quantitative analysis by densitometry showed a 149 and 166% increase in pro alpha 1(I) and pro alpha 1(III) mRNA after 24 h of IGF-1 treatment, respectively. This effect seems to be specific as the abundance of mRNA for the pro alpha 2(I) chain of type I procollagen or TIMP-II was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

肥厚性瘢痕(HSc)常见于严重热损伤患者,其特征是细胞外基质(ECM)蛋白积聚,包括I型和III型胶原蛋白。在本研究中,我们检测了烧伤后HSc中IGF-1 mRNA转录本的存在情况和数量。斑点印迹实验结果显示,与同一患者的正常真皮相比,HSc组织中IGF-1 IIIRNA的表达增加了77.5%(100±8.15对177.5±19,p<0.01)。Northern印迹分析证实了IGF-1 cDNA的特异性。该cDNA显示出四种不同的转录本,表观大小分别为7.0、3.9、1.8和1.0 kb,与先前报道的相似。通过分析这种生长因子对真皮成纤维细胞中I型前胶原α1(I)链和III型前胶原α1(III)链mRNA表达的影响,研究了IGF-1可能的促纤维化作用。IGF-1早在6小时就增加了这些转录本的表达,在24小时时作用最大。通过光密度测定法进行的定量分析显示,IGF-1处理24小时后,α1(I)和α1(III)mRNA分别增加了149%和166%。这种作用似乎具有特异性,因为I型前胶原α2(I)链或TIMP-II的mRNA丰度没有变化。(摘要截短于250字)

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