title: Hyaluronan-CD44-ERK1/2 regulate human aortic smooth muscle cell motility during aging.
abstract: The glycosaminoglycan hyaluronan (HA) modulates cell proliferation and migration, and it is involved in several human vascular pathologies including atherosclerosis and vascular restenosis. During intima layer thickening, HA increases dramatically in the neointima extracellular matrix. Aging is one of the major risk factors for the insurgence of vascular diseases, in which smooth muscle cells (SMCs) play a role by determining neointima formation through their migration and proliferation. Therefore, we established an in vitro aging model consisting of sequential passages of human aortic smooth muscle cells (AoSMCs). Comparing young and aged cells, we found that, during the aging process in vitro,HA synthesis significantly increases, as do HA synthetic enzymes (i.e. HAS2 and HAS3), the precursor synthetic enzyme (UDP-glucose dehydrogenase), and the HA receptor CD44. In aged cells, we also observed increased CD44 signaling that consisted of higher levels of phosphorylated MAP kinase ERK1/2. Further, aged AoSMCs migrated faster than young cells, and such migration could be modulated by HA, which alters the ERK1/2 phosphorylation. HA oligosaccharides of 6.8 kDa and an anti-CD44 blocking antibody prevented ERK1/2 phosphorylation and inhibited AoSMCs migration. These results indicate that, during aging, HA can modulate cell migration involving CD44-mediated signaling through ERK1/2. These data suggest that age-related HA accumulation could promote SMC migration and intima thickening during vascular neointima formation.
authors: Dip. di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi dell'Insubria, via J. H. Dunant 5, 21100 Varese, Italy.
authors: Davide
authors: D
authors: Vigetti
authors: Manuela
authors: M
authors: Viola
authors: Eugenia
authors: E
authors: Karousou
authors: Manuela
authors: M
authors: Rizzi
authors: Paola
authors: P
authors: Moretto
authors: Anna
authors: A
authors: Genasetti
authors: Moira
authors: M
authors: Clerici
authors: Vincent C
authors: VC
authors: Hascall
authors: Giancarlo
authors: G
authors: De Luca
authors: Alberto
authors: A
authors: Passi
mesh_terms: D000293:Adolescent; D000375:Aging / Q000502:physiology*; D001483:Base Sequence; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D017931:DNA Primers; D020869:Gene Expression Profiling; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology*; D006820:Hyaluronic Acid / Q000502:physiology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*
chemical_list: D017931:DNA Primers; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3