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

Citations Over TimeTop 12% of 2018 papers

Abstract

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.

Related Papers

• → Differential expression of TGF-β isoforms by normal and inflammatory bowel disease intestinal myofibroblasts(2002)155 cited
• → The role of transforming growth factor beta in Dupuytren's disease(1996)140 cited
• → Molecular analysis of the TGF-beta controlled gene expression program in chicken embryo dermal myofibroblasts(2012)23 cited
• → Site-directed mutagenesis of glycosylation sites in the transforming growth factor-beta 1 (TGF beta 1) and TGF beta 2 (414) precursors and of cysteine residues within mature TGF beta 1: effects on secretion and bioactivity(1992)27 cited
• → Myofibroblast differentiation and TGF-b1 signalling is affected in syndecan-4 deficient fibroblasts(2004)