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

Kelly A Correll,Douglas Curran-Everett,Karen E Edeen,Robert J Mason,Benjamin L Edelman,Thomas Danhorn,Rachel L Zemans,Amanda Mikels-Vigdal,Elizabeth F Redente

doi:10.14814/phy2.13794

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.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a devastating disease whose pathogenesis is not fully understood and has nearly a 50% 3-year mortality rate (Ley et al 2011; Nalysnyk et al 2012)
Since TGF beta is critical in the pathogenesis of IPF and hepatocyte growth factor (HGF), FGF7, and FGF10 are important in alveolar epithelial repair, we evaluated the effect of TGF beta on regulating HGF, FGF7, and FGF10 in both control and IPF human fibroblasts
We evaluated the effect of TGF beta on the expression of smooth muscle actin and genes related to the extracellular matrix to confirm previously published findings

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a devastating disease whose pathogenesis is not fully understood and has nearly a 50% 3-year mortality rate (Ley et al 2011; Nalysnyk et al 2012). Most reports on TGF beta have focused on matrix production by fibroblasts and surfactant production by alveolar type II cells. TGF beta delivered by an adenoviral vector has been shown to produce extensive pulmonary fibrosis in experimental animals (Sime et al 1997). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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