title: Purinergic signaling in wound healing and airway remodeling.
abstract: Airway epithelia are continuously damaged by airborne pollutants, pathogens and allergens, and they rely on intrinsic mechanisms to restore barrier integrity. Epithelial repair is a multi-step process including cell migration into the wounded area, proliferation, differentiation and matrix deposition. Each step requires the secretion of various molecules, including growth factors, integrins and matrix metalloproteinases. Evidence is emerging that purinergic signaling promotes repair in human airway epithelia. An injury induces ATP release, which binds P2Y(2) receptors (P2Y(2)Rs) to initiate protein kinase C (PKC)-dependent oxidative activation of TNFα-converting enzyme (TACE), which then releases the membrane-bound ligands of the epidermal growth factor receptor (EGFR). The P2Y(2)R- and EGFR-dependent signaling cascades converge to induce mediator release, whereas the latter also induces cytoskeletal rearrangement for cell migration and proliferation. Similar roles for purinergic signaling are reported in pulmonary endothelial cells, smooth muscle cells and fibroblasts. In chronic airway diseases, the aberrant regulation of extracellular purines is implicated in the development of airway remodeling by mucus cell metaplasia and hypersecretion, excess collagen deposition, fibrosis and neovascularization. This chapter describes the crosstalk between these signaling cascades and discusses the impact of deregulated purinergic signaling in chronic lung diseases.
authors.affiliation: Department of Pathology, University of Vermont, Burlington, VT, USA, albert.van-der-vliet@uvm.edu.
authors.forename: Albert
authors.initials: A
authors.lastname: van der Vliet
authors.forename: Peter F
authors.initials: PF
authors.lastname: Bove
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D011687:Purines / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014945:Wound Healing
chemical_list: D011687:Purines; D011983:Receptors, Purinergic