title: ERK, JNK, and p38 MAP kinases differentially regulate proliferation and migration of phenotypically distinct smooth muscle cell subtypes.
abstract: Proliferation and migration of vascular smooth muscle cells (SMCs) are important processes involved in the pathogenesis of vascular disorders such as atherosclerosis and post-angioplasty restenosis. Here we demonstrate that proliferation and migration of specific SMC subtypes is mitogen-activated protein (MAP) kinase-dependent. WKY12-22 SMCs derived from the aortae of 12 day-old pup rats proliferate and migrate faster than WKY3M-22 SMCs derived from the aortae of adult rats. WKY12-22 and WKY3M-22 cells equally expressed the active forms of phospho (Thr(183)/Tyr(185))-c-Jun N-terminal kinase (JNK) and phospho (Tyr(182))-p38, whereas the activity of extracellular signal-regulated kinase (ERK) was greater in WKY12-22 cells compared with WKY3M-22 cells. Proliferation of both SMC subtypes was attenuated by PD98059, SP600125 and SB202190, inhibitors of ERK, JNK, and p38, respectively. However, inhibition of PD98059 had a more profound effect on WKY12-22 SMCs. Furthermore, migration of WKY12-22 and WKY3M-22 cells was inhibited by SP600125 and SB202190, however, PD98059 failed to influence migration of either SMC subtype. Hence, migration of both SMC subtypes is JNK- and p38-dependent, but not ERK-dependent. These findings demonstrate that SMC heterogeneity is mediated, at least in part, by the activity of specific MAP kinase subtypes.
authors.affiliation: Centre for Vascular Research, The University of New South Wales, Australia.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Kavurma
authors.forename: Levon M
authors.initials: LM
authors.lastname: Khachigian
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010641:Phenotype; D051381:Rats
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one