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http://dx.doi.org/10.3904/kjim.2014.29.3.281

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)
Publication Information
The Korean journal of internal medicine / v.29, no.3, 2014 , pp. 281-290 More about this Journal
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
Transforming growth factor beta1; Pulmonary fibrosis; Response modifiers; Amphiregulin; Chitotriosidase;
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