TGF beta inhibits HGF, FGF7, and FGF10 expression in normal and IPF lung fibroblasts.

TGF beta inhibits HGF, FGF7, and FGF10 expression in normal and IPF lung fibroblasts.
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DOI:
10.14814/phy2.13794
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发表时间:
2018-08
影响因子:
2.5
通讯作者:
Mason RJ
Mason RJ
中科院分区:
其他
文献类型:
--
作者:
Correll KA;Edeen KE;Redente EF;Zemans RL;Edelman BL;Danhorn T;Curran-Everett D;Mikels-Vigdal A;Mason RJ

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转化生长因子β是一种多功能细胞因子,在肺纤维化的发病机制中起重要作用。转化生长因子β刺激成纤维细胞中的平滑肌肌动蛋白和细胞外基质基因表达的能力已经确立。在这篇报道中,我们评估了转化生长因子β对肺泡上皮细胞重要生长和生存因子HGF、Fgf7(KGF)和FGF10表达的影响。这些生长因子对于维持II型细胞和肺损伤后上皮的恢复是重要的。在正常血清补充或血清撤除条件下,转化生长因子β抑制成纤维细胞HGF、Fgf7和FGF10的表达。我们用对照和IPF成纤维细胞对转化生长因子β的反应的全基因组RNA测序证实了这些观察结果。总的来说,IPF成纤维细胞的基因表达与对照成纤维细胞相似。HGF、Fgf7和FGF10的表达减少是转化生长因子β损害肺损伤后上皮愈合和促进纤维化的另一种方式。
TGF beta is a multifunctional cytokine that is important in the pathogenesis of pulmonary fibrosis. The ability of TGF beta to stimulate smooth muscle actin and extracellular matrix gene expression in fibroblasts is well established. In this report, we evaluated the effect of TGF beta on the expression of HGF, FGF7 (KGF), and FGF10, important growth and survival factors for the alveolar epithelium. These growth factors are important for maintaining type II cells and for restoration of the epithelium after lung injury. Under conditions of normal serum supplementation or serum withdrawal TGF beta inhibited fibroblast expression of HGF, FGF7, and FGF10. We confirmed these observations with genome wide RNA sequencing of the response of control and IPF fibroblasts to TGF beta. In general, gene expression in IPF fibroblasts was similar to control fibroblasts. Reduced expression of HGF, FGF7, and FGF10 is another means whereby TGF beta impairs epithelial healing and promotes fibrosis after lung injury.