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首页> 外文期刊>Investigative ophthalmology & visual science >Connective tissue growth factor expression and action in human corneal fibroblast cultures and rat corneas after photorefractive keratectomy.
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Connective tissue growth factor expression and action in human corneal fibroblast cultures and rat corneas after photorefractive keratectomy.

机译：屈光性角膜切除术后人角膜成纤维细胞和大鼠角膜中结缔组织生长因子的表达和作用。

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PURPOSE. Connective tissue growth factor (CTGF) has been linked to fibrosis in several tissues. In this study, the interactions between CTGF and transforming growth factor (TGF)-beta were assessed in human corneal fibroblasts, and the levels and location of CTGF protein and mRNA were measured during healing of excimer laser ablation wounds in rat corneas. METHODS. Human corneal fibroblasts were incubated with TGF-beta1, -beta2, and -beta3 isoforms, and CTGF mRNA and protein were measured. CTGF was immunolocalized in the cultured fibroblasts by using a specific antibody. Regulation of collagen synthesis by TGF-beta and CTGF was assessed in human corneal fibroblasts with a neutralizing antibody and an antisense oligonucleotide to CTGF. CTGF mRNA and protein were measured in rat corneas up to day 21 after excimer ablation of the cornea. CTGF protein was immunolocalized in rat corneas after photorefractive keratectomy (PRK), and the presence of CTGF mRNA and protein in ex vivo rat corneal scrapings was established. RESULTS. All three TGF-beta isoforms stimulated expression of CTGF in human corneal fibroblasts, and CTGF was immunolocalized in the cells. Both TGF-beta and CTGF increased collagen synthesis in corneal fibroblasts. Furthermore, CTGF antibody or antisense oligonucleotide blocked TGF-beta-stimulated collagen synthesis. CTGF protein and mRNA increased in rat corneas through day 21 after PRK. CTGF expression was also detected in ex vivo scrapings of rat corneas. CONCLUSIONS. These data demonstrate that CTGF is expressed by corneal cells after stimulation by TGF-beta, that CTGF expression increases significantly during corneal wound healing, and that CTGF mediates the effects of TGF-beta induction of collagen synthesis by corneal fibroblasts. These data support the hypothesis that CTGF promotes corneal scar formation and imply that regulating CTGF synthesis and action may be an important goal for reducing corneal scarring.
机译：目的。结缔组织生长因子（CTGF）与几种组织的纤维化有关。在这项研究中，在人角膜成纤维细胞中评估了CTGF和转化生长因子（TGF）-β之间的相互作用，并在大鼠角膜准分子激光消融伤口愈合期间测量了CTGF蛋白和mRNA的水平和位置。方法。将人角膜成纤维细胞与TGF-beta1，-beta2和-beta3亚型一起孵育，并测量CTGF mRNA和蛋白质。通过使用特异性抗体将CTGF免疫定位在培养的成纤维细胞中。使用中和抗体和CTGF的反义寡核苷酸评估了人角膜成纤维细胞中TGF-β和CTGF对胶原蛋白合成的调控。在准分子切除角膜后直至第21天，在大鼠角膜中测量CTGF mRNA和蛋白质。在屈光性角膜切除术（PRK）后，将CTGF蛋白免疫定位在大鼠角膜中，并确定离体大鼠角膜刮除物中CTGF mRNA和蛋白的存在。结果。所有三种TGF-β亚型均刺激人角膜成纤维细胞中CTGF的表达，并且CTGF在细胞中进行了免疫定位。 TGF-β和CTGF均可增加角膜成纤维细胞中胶原的合成。此外，CTGF抗体或反义寡核苷酸可阻断TGF-β刺激的胶原蛋白合成。 PRK后第21天，大鼠角膜CTGF蛋白和mRNA的表达增加。在大鼠角膜的离体刮擦中也检测到CTGF表达。结论。这些数据表明，CTGF在TGF-β刺激后由角膜细胞表达，CTGF表达在角膜伤口愈合过程中显着增加，并且CTGF介导TGF-β诱导角膜成纤维细胞合成胶原。这些数据支持CTGF促进角膜瘢痕形成的假设，并暗示调节CTGF​​的合成和作用可能是减少角膜瘢痕形成的重要目标。

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