The Roles of Apoptosis in Wound Healing and Pulmonary Fibrosis

Authors: Gharaee-Kermani M; Phan S. H

Source: Drug Design Reviews - Online, Volume 1, Number 4, October 2004 , pp. 313-323(11)

Publisher: Bentham Science Publishers

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Abstract:

Apoptosis has fundamental significance in both normal tissue homeostasis and pathophysiological processes such as wound healing, inflammation, and fibrosis. Failure to clear unwanted cells by apoptosis will prolong inflammation due to the release of their toxic contents. In contrast, excessive apoptosis may cause diseases. Examination of lung biopsies from patients with idiopathic pulmonary fibrosis and animal models of lung fibrosis have found apoptotic cells associated with fibrotic lesions. Transforming growth factor- bgr

1 (TGF-

1) has important roles in lung fibrosis and has the potential to induce apoptosis of lung epithelial cells in vitro and in vivo . Administration of TGF- bgr

1 could enhance Fasmediated epithelial cell apoptosis and lung injury via caspase-3 activation, and caspase inhibitors can prevent the development of fibrosis. Recent progress in understanding the mechanisms of lung fibrosis and regulation of apoptosis in various cell types in lung tissue leads us to expect that inhibitors of apoptosis can prevent subsequent increases in collagen levels and may also be useful as novel therapeutic agents in controlling undesirable fibrosis. In this review, the role of apoptosis in the pathogenesis and resolution of fibrotic lesions will be summarized and highlighted, with more detailed discussion on regulation and signal transduction pathway of apoptosis in lung fibrosis.

Keywords: lung fibrosis; inflammation; cytokine; apoptosis

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1567269043390717

Affiliations: 1: 5259 LSI, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-2216

Publication date: 2004-10-01