title: Calcium signalling in wound-responsive normal human urothelial cell monolayers.
abstract: Epithelial tissue repair requires coordination of migratory and proliferative activity both adjacent to and remote from the wound edge. Although calcium signalling is implicated, the specific mechanisms are poorly understood. This study characterises the calcium signal invoked in response to scratch wounding of normal human urothelial (NHU) cells and relates it to the localised cellular response. Immediately after wounding of confluent NHU cell monolayers, cells adjacent to the wound edge showed a sustained (>30 min) rise in [Ca(2+)](i), while there was an independent, but simultaneous calcium wave that propagated out from the wound edge. The transient signal involved release of calcium from intracellular stores and was not mediated via gap junctions, but by diffusion of extracellular agonists. We demonstrated that ATP was partially responsible for the initiation and propagation of the calcium wave and showed that the calcium release mechanism was mediated in part via activation of inositol-1,4,5-triphosphate (IP(3)) receptors. By contrast, the sustained calcium signal originated from the extracellular milieu and correlated with an increased rate of migration by these cells. The work presented here provides supportive evidence that the calcium signature, defined by its temporal and amplitude characteristics, is important in co-ordinating the response of cells within an epithelial cell monolayer after wounding.
authors.affiliation: Jack Birch Unit of Molecular Carcinogenesis, Department of Biology, University of York YO10 5YW, UK.
authors.forename: Saqib
authors.initials: S
authors.lastname: Shabir
authors.forename: Jennifer
authors.initials: J
authors.lastname: Southgate
mesh_terms: D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D019459:Urothelium / Q000166:cytology* / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D002118:Calcium