Human epithelial airway cells constitutively produce molecules involved in initiating epithelial proliferation and differentiation — the growth factor heregulin, and its receptors; erbB2, erbB3 and erbB4. Under normal conditions airway epithelium has a low rate of cell division, but how proliferation is initiated following a mechanical disruption of epithelial lining has been unclear. In the March 20 Nature, Paola D. Vermeer and colleagues at the Roy J. and Lucille A. Carver College of Medicine, Iowa City, US, show that the physical segregation of receptor and ligand regulates epithelial growth factor receptor activation and epithelial proliferation (Nature, 422:322-326, March 20, 2003).

Vermeer et al. analyzed cell cultures of human airway epithelia derived from lungs removed for organ donation. They observed that heregulin-α was present exclusively in the apical membrane and the overlying airway surface liquid, physically separated heregulin-α from the basolateral membrane where erbB2, 3 and...

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