Modifiers of TGF-b1 effector function as novel therapeutic targets of pulmonary fibrosis

• Published in: The Korean journal of internal medicine 2014, 29(3), , pp.281-290
• Main Authors: 이창민, 박진욱, 조원경, Yang Zhou, 한보람, 윤평오, 채제욱, Jack A Elias, 이천근
• Format: Article
• Language: English
• Subjects: 내과학
• ISSN: 1226-3303; 2005-6648
• DOI: 10.3904/kjim.2014.29.3.281

Pulmonary fibrosis is a fatal progressive disease with no effective therapy. Transforminggrowth factor (TGF)-b1 has long been regarded as a central mediator oftissue fibrosis that involves multiple organs including skin, liver, kidney, and lung. Thus, TGF-b1 and its signaling pathways have been attractive therapeutic targetsfor the development of antifibrotic drugs. However, the essential biological functionsof TGF-b1 in maintaining normal immune and cellular homeostasis significantlylimit the effectiveness of TGF-b1-directed therapeutic approaches. Thus,targeting downstream mediators or signaling molecules of TGF-b1 could be an alternativeapproach that selectively inhibits TGF-b1-stimulated fibrotic tissue responsewhile preserving major physiological function of TGF-b1. Recent studiesfrom our laboratory revealed that TGF-b1 crosstalk with epidermal growth factorreceptor (EGFR) signaling by induction of amphiregulin, a ligand of EGFR, plays acritical role in the development or progression of pulmonary fibrosis. In addition,chitotriosidase, a true chitinase in humans, has been identified to have modulatingcapacity of TGF-b1 signaling as a new biomarker and therapeutic target of scleroderma-associated pulmonary fibrosis. These newly identified modifiers of TGF-b1effector function significantly enhance the effectiveness and flexibility in targetingpulmonary fibrosis in which TGF-b1 plays a significant role. KCI Citation Count: 33