Modifiers of TGF-beta1 effector function as novel therapeutic targets of pulmonary fibrosis
The Korean Journal of Internal Medicine
;
: 281-290, 2014.
Article
in English
| WPRIM
| ID: wpr-62924
ABSTRACT
Pulmonary fibrosis is a fatal progressive disease with no effective therapy. Transforming growth factor (TGF)-beta1 has long been regarded as a central mediator of tissue fibrosis that involves multiple organs including skin, liver, kidney, and lung. Thus, TGF-beta1 and its signaling pathways have been attractive therapeutic targets for the development of antifibrotic drugs. However, the essential biological functions of TGF-beta1 in maintaining normal immune and cellular homeostasis significantly limit the effectiveness of TGF-beta1-directed therapeutic approaches. Thus, targeting downstream mediators or signaling molecules of TGF-beta1 could be an alternative approach that selectively inhibits TGF-beta1-stimulated fibrotic tissue response while preserving major physiological function of TGF-beta1. Recent studies from our laboratory revealed that TGF-beta1 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-beta1 signaling as a new biomarker and therapeutic target of scleroderma-associated pulmonary fibrosis. These newly identified modifiers of TGF-beta1 effector function significantly enhance the effectiveness and flexibility in targeting pulmonary fibrosis in which TGF-beta1 plays a significant role.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pulmonary Fibrosis
/
Drug Design
/
Signal Transduction
/
Receptors, Transforming Growth Factor beta
/
Receptor Cross-Talk
/
Transforming Growth Factor beta1
/
Molecular Targeted Therapy
/
ErbB Receptors
/
Hexosaminidases
/
Lung
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
The Korean Journal of Internal Medicine
Year:
2014
Type:
Article
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