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TGF-β: Titan of Lung Fibrogenesis

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Date 2013 Nov 5
PMID 24187529
Citations 80
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Abstract

Pulmonary fibrosis is characterized by epithelial cell injury, accumulation of myofibroblasts, and excessive deposition of collagen and other extracellular matrix elements, leading to loss of pulmonary function. Studies in both humans and animal models strongly suggest that TGF-β1 plays a pivotal role in the pathogenesis of pulmonary fibrosis. This review will first give an overview of TGF-β signaling and the effects of its inhibition on lung fibrogenesis. This overview includes information on TGF-β signal transduction pathways, the importance of TGF-β in the accumulation of myofibroblasts, the role of TGF-β in epithelial injury and apoptosis, the role of TGF-β in extracellular matrix remodeling, and the effects of inhibiting TGF-β signaling in animal models of lung fibrosis. Subsequently this review will highlight recent advances in two areas of particular interest to our research group: (1) TGF-β and proteoglycans; (2) TGF-β and histone deacetylases. Although our understanding of the role of TGF-β and its mechanisms of action in lung fibrogenesis has increased dramatically in recent years, there is still much to be learned about this important molecule, especially how TGF-β function is modulated , and its complex interactions with other factors expressed during lung injury and repair. Research in these areas will help identify novel therapeutic targets for the treatment of pulmonary fibrosis that will hopefully improve the prognosis of this devastating illness.

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References
1.
Uhal B, Joshi I, Hughes W, Ramos C, Pardo A, Selman M . Alveolar epithelial cell death adjacent to underlying myofibroblasts in advanced fibrotic human lung. Am J Physiol. 1998; 275(6):L1192-9. DOI: 10.1152/ajplung.1998.275.6.L1192. View

2.
McKeown S, Richter A, OKane C, McAuley D, Thickett D . MMP expression and abnormal lung permeability are important determinants of outcome in IPF. Eur Respir J. 2008; 33(1):77-84. DOI: 10.1183/09031936.00060708. View

3.
Yamada M, Kuwano K, Maeyama T, Yoshimi M, Hamada N, Fukumoto J . Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis. J Clin Pathol. 2006; 60(8):916-20. PMC: 1994490. DOI: 10.1136/jcp.2006.039396. View

4.
Sheppard D . Transforming growth factor beta: a central modulator of pulmonary and airway inflammation and fibrosis. Proc Am Thorac Soc. 2006; 3(5):413-7. PMC: 2658705. DOI: 10.1513/pats.200601-008AW. View

5.
KUHN 3rd C, Boldt J, King Jr T, Crouch E, Vartio T, McDonald J . An immunohistochemical study of architectural remodeling and connective tissue synthesis in pulmonary fibrosis. Am Rev Respir Dis. 1989; 140(6):1693-703. DOI: 10.1164/ajrccm/140.6.1693. View