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Sci. STKE, 18 March 2003
Vol. 2003, Issue 174, p. tw113
[DOI: 10.1126/stke.2003.174.tw113]

EDITORS' CHOICE

TGF-β TGF-β Activation in Lungs Leads to Emphysema

The hallmarks of emphysema include gradual breakdown of connective tissue in the lung and decreased airflow. Contributing factors such as cytokines, growth factors, and metalloproteinases have been proposed on the basis of rodent models. Now, Morris et al. add transforming growth factor-β (TGF-β) to this list. When the latency-associated peptides of TGF-β bind to the integrin αvβ6 on lung epithelial cells, TGF-β becomes activated and hence, available to activate cognate receptors on macrophages in the lung. This reduces production of the matrix metalloproteinase MMP12 in macrophages. MMP12 degrades elastic fibers of lung tissue and mice lacking this enzyme do not develop emphysema when exposed to cigarette smoke. Mice lacking αvβ6 developed emphysema, but additional loss of MMP12 in these mice reversed this phenotype. Expression of activated TGF-β in the lungs of αvβ6-null mice also eliminated lung inflammation. This pathway of TGF-β activation in the lungs may offer another approach to preventing emphysema in humans.

D. G. Morris, X. Huang, N. Kaminski, Y. Wang, S. D. Shapiro, G. Dolganov, A. Glick, D. Sheppard, Loss of integrin αvβ6-mediated TGF-β activation causes Mmp12-dependent emphysema. Nature 422, 169-173 (2003). [Online Journal]

Citation: TGF-β Activation in Lungs Leads to Emphysema. Sci. STKE 2003, tw113 (2003).


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