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The role of apoptosis in pulmonary fibrosis

CORRESPONDENCE: B. D. Uhal, Dept of Physiology, Michigan State University, 3197 BPS Building, East Lansing, MI 48824, USA. Fax: 1 5173555125. E-mail: uhal{at}msu.edu

Apoptosis has been defined as "gene-directed cellular self-destruction" and is an active process that is tightly regulated by a number of gene products, which promote or block cell death. Apoptotic death can be triggered by a wide variety of stimuli and, importantly, not all cells necessarily undergo apoptosis in response to the same stimulus. Abnormal regulation of apoptosis has been implicated in a wide range of diseases and approaches to modifying apoptosis represent important future therapeutic strategies.

Idiopathic pulmonary fibrosis (IPF) is a progressive and relentless disease involving scarring of the lung, which has been recognised as the most lethal interstitial lung disease. In the lungs of IPF patients, increased epithelial apoptosis, together with decreased apoptosis of myofibroblasts, represents persistent findings (particularly in areas of collagen deposition) supporting an interaction between altered apoptosis and the pathogenesis of the disease.

Data from human tissues and animal models are refining current knowledge of the processes involved in this pathogenesis. This has challenged the dogma that IPF is purely a disease of unresolved inflammation by emphasising the central roles played by the alveolar epithelial cell and myofibroblasts and, as part of that role, the importance of altered apoptosis.

Evidence suggests blockade of epithelial cell apoptosis can prevent subsequent collagen deposition, and induction of myofibroblast apoptosis, at least theoretically, would be expected to resolve ongoing fibrosis. These two concepts raise the prospect of therapeutic intervention aimed at modifying apoptosis and, thus, fibrosis in idiopathic pulmonary fibrosis.

KEYWORDS: Angiotensin, epithelium, lung, myofibroblasts