The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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Modifiers of TGF-${\beta}1$ effector function as novel therapeutic targets of pulmonary fibrosis

  • Lee, Chang-Min (Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine) ;
  • Park, Jin Wook (Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine) ;
  • Cho, Won-Kyung (Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine) ;
  • Zhou, Yang (Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine) ;
  • Han, Boram (Bioneer Corporation) ;
  • Yoon, Pyoung Oh (Bioneer Corporation) ;
  • Chae, Jeiwook (Bioneer Corporation) ;
  • Elias, Jack A. (Dean of Medicine and Biological Science, Brown University, Warren Alpert School of Medicine) ;
  • Lee, Chun Geun (Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine)
  • Received : 2014.03.31
  • Accepted : 2014.04.02
  • Published : 2014.05.01
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Abstract

Pulmonary fibrosis is a fatal progressive disease with no effective therapy. Transforming growth factor (TGF)-${\beta}1$ has long been regarded as a central mediator of tissue fibrosis that involves multiple organs including skin, liver, kidney, and lung. Thus, TGF-${\beta}1$ and its signaling pathways have been attractive therapeutic targets for the development of antifibrotic drugs. However, the essential biological functions of TGF-${\beta}1$ in maintaining normal immune and cellular homeostasis significantly limit the effectiveness of TGF-${\beta}1$-directed therapeutic approaches. Thus, targeting downstream mediators or signaling molecules of TGF-${\beta}1$ could be an alternative approach that selectively inhibits TGF-${\beta}1$-stimulated fibrotic tissue response while preserving major physiological function of TGF-${\beta}1$. Recent studies from our laboratory revealed that TGF-${\beta}1$ crosstalk with epidermal growth factor receptor (EGFR) signaling by induction of amphiregulin, a ligand of EGFR, plays a critical role in the development or progression of pulmonary fibrosis. In addition, chitotriosidase, a true chitinase in humans, has been identified to have modulating capacity of TGF-${\beta}1$ signaling as a new biomarker and therapeutic target of scleroderma-associated pulmonary fibrosis. These newly identified modifiers of TGF-${\beta}1$ effector function significantly enhance the effectiveness and flexibility in targeting pulmonary fibrosis in which TGF-${\beta}1$ plays a significant role.

Keywords

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