Department of Pathology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
Clinics (Sao Paulo). 2012 Sep;67(9):1039-46. doi: 10.6061/clinics/2012(09)10.
This study sought to identify the relationship between fibroblast telomerase expression, myofibroblasts, and telomerase-mediated regulatory signals in idiopathic pulmonary fibrosis.
Thirty-four surgical lung biopsies, which had been obtained from patients with idiopathic pulmonary fibrosis and histologically classified as usual interstitial pneumonia, were examined. Immunohistochemistry was used to evaluate fibroblast telomerase expression, myofibroblast α-smooth muscle actin expression and the tissue expression of inter leu kin-4, transforming growth factor-β, and basic fibroblast growth factor. The point-counting technique was used to quantify the expression of these markers in unaffected, collapsed, mural fibrosis, and honeycombing areas. The results were correlated to patient survival.
Fibroblast telomerase expression and basic fibroblast growth factor tissue expression were higher in collapsed areas, whereas myofibroblast expression and interleukine-4 tissue expression were higher in areas of mural fibrosis. Transforming growth factor-β expression was higher in collapsed, mural fibrosis and honeycombing areas in comparison to unaffected areas. Positive correlations were found between basic fibroblast growth factor tissue expression and fibroblast telomerase expression and between interleukin-4 tissue expression and myofibroblast α-smooth muscle actin expression. Negative correlations were observed between interleukin-4 expression and basic fibroblast growth factor tissue expression in areas of mural fibrosis. Myofibroblast α-smooth muscle actin expression and interleukin-4 tissue expression in areas of mural fibrosis were negatively associated with patient survival.
Fibroblast telomerase expression is higher in areas of early remodeling in lung tissues demonstrating typical interstitial pneumonia, whereas myofibroblast α-smooth muscle actin expression predominates in areas of late remodeling. These events seem to be regulated by basic fibroblast growth factor and interleukin-4 tissue expression, respectively.
本研究旨在确定特发性肺纤维化中成纤维细胞端粒酶表达、肌成纤维细胞以及端粒酶介导的调节信号之间的关系。
对 34 例经手术获得的特发性肺纤维化患者的肺组织活检标本进行研究，这些标本经组织学检查均被分类为寻常型间质性肺炎。采用免疫组织化学方法检测成纤维细胞端粒酶表达、肌成纤维细胞α-平滑肌肌动蛋白表达以及组织中白细胞介素-4、转化生长因子-β和碱性成纤维细胞生长因子的表达。采用点计数技术对这些标志物在未受影响区、塌陷区、壁层纤维化区和蜂窝织区的表达进行定量。并将结果与患者的生存情况进行相关性分析。
在塌陷区，成纤维细胞端粒酶表达和碱性成纤维细胞生长因子组织表达较高，而肌成纤维细胞表达和白细胞介素-4组织表达在壁层纤维化区较高。与未受影响区相比，转化生长因子-β在塌陷区、壁层纤维化区和蜂窝织区的表达较高。碱性成纤维细胞生长因子组织表达与成纤维细胞端粒酶表达之间以及白细胞介素-4组织表达与肌成纤维细胞α-平滑肌肌动蛋白表达之间存在正相关。在壁层纤维化区，白细胞介素-4表达与碱性成纤维细胞生长因子组织表达之间存在负相关。壁层纤维化区的肌成纤维细胞α-平滑肌肌动蛋白表达和白细胞介素-4组织表达与患者的生存呈负相关。
在表现为典型间质性肺炎的肺组织早期重塑区，成纤维细胞端粒酶表达较高，而在晚期重塑区，肌成纤维细胞α-平滑肌肌动蛋白表达占主导地位。这些事件似乎分别受到碱性成纤维细胞生长因子和白细胞介素-4组织表达的调节。
