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Recent advances in molecular targets and treatment of idiopathic pulmonary fibrosis: focus on TGFbeta signaling and the myofibroblast

gdlizhaokun 添加于 2009-7-10 21:24 | 1475 次阅读 | 0 个评论

作者
Gharaee-Kermani M, Hu B, Phan SH, Gyetko MR
摘要
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.
详细资料
- 关键词: Animals; Cell Differentiation; Epithelial Cells/*pathology; Extracellular Matrix/genetics/metabolism; Fibroblasts/*pathology; Gene Expression Regulation; Humans; Idiopathic Pulmonary Fibrosis/*drug therapy/*physiopathology; Pulmonary Alveoli/*pathology; Transforming Growth Factor beta/antagonists & inhibitors/genetics/*metabolism
- 文献种类:期刊
- 期刊名称: Current Medicinal Chemistry
- 期刊缩写: Curr Med Chem
- 期卷页: 2009年第16卷第11期 1400-1417页
- 地址: 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.edu
- ISBN: 0929-8673
- 备注:PMID:19355895
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