title: Smooth muscle cell response to mechanical injury involves intracellular calcium release and ERK1/ERK2 phosphorylation.
abstract: We have investigated possible signaling pathways coupled to injury-induced ERK1/2 activation and the subsequent initiation of vascular rat smooth muscle cell migration and proliferation. Aortic smooth muscle cells were cultured to confluency and subjected to in vitro injury under serum-free conditions. In fluo-4-loaded cells, injury induced a rapid wave of intracellular Ca(2+) release that propagated about 200 microm in radius from the injured zone, reached a peak in about 20 s, and subsided to the baseline within 2 min. The wave was abolished by prior treatment with the sarcoplasmic reticulum ATPase inhibitor thapsigargin, but not by omission of extracellular Ca(2+). ERK1/2 activation reached a peak at 10 min after injury and was inhibited by the MEK1 inhibitor PD98059, as well as by thapsigargin, fluphenazine, genistein, and the Src inhibitor PP2. These inhibitors also reduced [(3)H]thymidine incorporation and migration of cells into the injured area determined at 48 h after injury. These results show that mechanical injury to vascular smooth muscle cells induces a Ca(2+) wave which is dependent on intracellular Ca(2+) release. Furthermore, the injury activates ERK1/2 phosphorylation as well as cell migration and replication.
authors.affiliation: Section for Connective Tissue Biology, Department of Cell and Molecular Biology, Lund University, S-221 84 Lund, Sweden. Sara.Moses@medkem.lu.se
authors.forename: S
authors.initials: S
authors.lastname: Moses
authors.forename: K
authors.initials: K
authors.lastname: Dreja
authors.forename: A
authors.initials: A
authors.lastname: Lindqvist
authors.forename: C
authors.initials: C
authors.lastname: Lövdahl
authors.forename: P
authors.initials: P
authors.lastname: Hellstrand
authors.forename: A
authors.initials: A
authors.lastname: Hultgårdh-Nilsson
mesh_terms: D000818:Animals; D001158:Arteries / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005476:Fluphenazine / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000442:Octanols / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D019284:Thapsigargin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D002147:Calmodulin; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007476:Ionophores; D000442:Octanols; D000001:Calcimycin; D004533:Egtazic Acid; D015759:Ionomycin; D019284:Thapsigargin; D004247:DNA; D014700:Verapamil; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D005476:Fluphenazine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium