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Recent advances in molecular targets and treatment of idiopathic pulmonary fibrosis: focus on TGFbeta signaling and the myofibroblast.
Curr Med Chem 2009; 16(11):1400-17CM

Abstract

Idiopathic Pulmonary Fibrosis (IPF) is characterized by injury and loss of lung epithelial cells, accumulation of fibroblasts/myofibroblasts and abnormal remodeling of the lung parenchyma. The prognosis for IPF patients is poor and current therapies are largely ineffective in preventing respiratory failure. Current therapeutic approaches target epithelial cell replacement, manipulation of fibroblasts/myofibroblasts, modulation of procoagulant/fibrinolytic activities, cytokine and growth factor production, angiogenesis, and reduction of oxidative stress. Myofibroblasts are the primary effector cells in fibrosis. These cells may be derived by the activation and proliferation of resident lung fibroblasts, from epithelial-mesenchymal transition (EMT), or through recruitment of circulating fibrocytes. Transforming growth factor beta (TGFbeta) is a profibrotic factor that increases fibroblast proliferation, stimulates the synthesis and deposition of connective tissue, and inhibits connective tissue breakdown. TGFbeta acts through the promoter of the type 1 collagen gene causing increased collagen synthesis. In addition, TGFbeta induces EMT in alveolar epithelial cells (AECs) in vitro and in vivo. AECs exhibit substantial plasticity and may serve as a source of fibroblasts and/or myofibroblasts in lung fibrosis. Therapeutic interventions interfering with the pathways that lead to myofibroblast expansion and AEC apoptosis should be of considerable benefit in the treatment of IPF. This review will focus on the critical role of TGFbeta on AECs EMT and myofibroblasts in the development of fibrosis.

Authors+Show Affiliations

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ann Arbor Veterans Affairs Medical Center and University of Michigan Medical School, 2215 Fuller Road, 11 R, Ann Arbor, MI 48105, USA. nazy@umich.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Review

Language

eng

PubMed ID

19355895

Citation

Gharaee-Kermani, M, et al. "Recent Advances in Molecular Targets and Treatment of Idiopathic Pulmonary Fibrosis: Focus On TGFbeta Signaling and the Myofibroblast." Current Medicinal Chemistry, vol. 16, no. 11, 2009, pp. 1400-17.
Gharaee-Kermani M, Hu B, Phan SH, et al. Recent advances in molecular targets and treatment of idiopathic pulmonary fibrosis: focus on TGFbeta signaling and the myofibroblast. Curr Med Chem. 2009;16(11):1400-17.
Gharaee-Kermani, M., Hu, B., Phan, S. H., & Gyetko, M. R. (2009). Recent advances in molecular targets and treatment of idiopathic pulmonary fibrosis: focus on TGFbeta signaling and the myofibroblast. Current Medicinal Chemistry, 16(11), pp. 1400-17.
Gharaee-Kermani M, et al. Recent Advances in Molecular Targets and Treatment of Idiopathic Pulmonary Fibrosis: Focus On TGFbeta Signaling and the Myofibroblast. Curr Med Chem. 2009;16(11):1400-17. PubMed PMID: 19355895.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recent advances in molecular targets and treatment of idiopathic pulmonary fibrosis: focus on TGFbeta signaling and the myofibroblast. AU - Gharaee-Kermani,M, AU - Hu,B, AU - Phan,S H, AU - Gyetko,M R, PY - 2009/4/10/entrez PY - 2009/4/10/pubmed PY - 2009/6/23/medline SP - 1400 EP - 17 JF - Current medicinal chemistry JO - Curr. Med. Chem. VL - 16 IS - 11 N2 - Idiopathic Pulmonary Fibrosis (IPF) is characterized by injury and loss of lung epithelial cells, accumulation of fibroblasts/myofibroblasts and abnormal remodeling of the lung parenchyma. The prognosis for IPF patients is poor and current therapies are largely ineffective in preventing respiratory failure. Current therapeutic approaches target epithelial cell replacement, manipulation of fibroblasts/myofibroblasts, modulation of procoagulant/fibrinolytic activities, cytokine and growth factor production, angiogenesis, and reduction of oxidative stress. Myofibroblasts are the primary effector cells in fibrosis. These cells may be derived by the activation and proliferation of resident lung fibroblasts, from epithelial-mesenchymal transition (EMT), or through recruitment of circulating fibrocytes. Transforming growth factor beta (TGFbeta) is a profibrotic factor that increases fibroblast proliferation, stimulates the synthesis and deposition of connective tissue, and inhibits connective tissue breakdown. TGFbeta acts through the promoter of the type 1 collagen gene causing increased collagen synthesis. In addition, TGFbeta induces EMT in alveolar epithelial cells (AECs) in vitro and in vivo. AECs exhibit substantial plasticity and may serve as a source of fibroblasts and/or myofibroblasts in lung fibrosis. Therapeutic interventions interfering with the pathways that lead to myofibroblast expansion and AEC apoptosis should be of considerable benefit in the treatment of IPF. This review will focus on the critical role of TGFbeta on AECs EMT and myofibroblasts in the development of fibrosis. SN - 0929-8673 UR - https://www.unboundmedicine.com/medline/citation/19355895/Recent_advances_in_molecular_targets_and_treatment_of_idiopathic_pulmonary_fibrosis:_focus_on_TGFbeta_signaling_and_the_myofibroblast_ L2 - http://www.eurekaselect.com/68992/article DB - PRIME DP - Unbound Medicine ER -