title: Fibroblast cytoskeletal remodeling induced by tissue stretch involves ATP signaling.
abstract: Fibroblasts in whole areolar connective tissue respond to static stretching of the tissue by expanding and remodeling their cytoskeleton within minutes both ex vivo and in vivo. This study tested the hypothesis that the mechanism of fibroblast expansion in response to tissue stretch involves extracellular ATP signaling. In response to tissue stretch ex vivo, ATP levels in the bath solution increased significantly, and this increase was sustained for 20 min, returning to baseline at 60 min. No increase in ATP was observed in tissue incubated without stretch or tissue stretched in the presence of the Rho kinase inhibitor Y27632. The increase in fibroblast cross sectional area in response to tissue stretch was blocked by both suramin (a purinergic receptor blocker) and apyrase (an enzyme that selectively degrades extracellular ATP). Furthermore, connexin channel blockers (octanol and carbenoxolone), but not VRAC (fluoxetine) or pannexin (probenecid) channel blockers, inhibited fibroblast expansion. Together, these results support a mechanism in which extracellular ATP signaling via connexin hemichannels mediate the active change in fibroblast shape that occurs in response to a static increase in tissue length.
authors: Department of Neurological Sciences, University of Vermont, Burlington, Vermont 05405, USA. helene.langevin@uvm.edu
authors: Helene M
authors: HM
authors: Langevin
authors: Takumi
authors: T
authors: Fujita
authors: Nicole A
authors: NA
authors: Bouffard
authors: Takahiro
authors: T
authors: Takano
authors: Cathryn
authors: C
authors: Koptiuch
authors: Gary J
authors: GJ
authors: Badger
authors: Maiken
authors: M
authors: Nedergaard
mesh_terms: D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D003238:Connective Tissue / Q000187:drug effects* / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D051379:Mice; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D013314:Stress, Mechanical; D013498:Suramin / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D000577:Amides; D011725:Pyridines; C108830:Y 27632; D013498:Suramin; D000255:Adenosine Triphosphate; D054460:rho-Associated Kinases; D002229:Carbenoxolone