Aortic smooth muscle cells migration and the role of metalloproteinases and hyaluronan.
Human aortic smooth muscle cells (AoSMCs) change their extracellular matrix composition during aging, with direct effects on cellular events and cell migration. For example, active matrix metalloproteinase-2 (MMP-2) is synthesized only by young AoSMCs, whereas aged cells produce only the inactive zymogen form. The pro-MMP-2 activation in young cells depends on an increase in membrane type 1 matrix metalloproteinase content. Furthermore, transcripts coding for tissue inhibitor of metalloproteinases (TIMPs) were upregulated in aged cells, and the increase of TIMPs also could prevent pro-MMP-2 activation. As consequence of these situations, young AoSMCs possess a higher migratory capability than aged cells on gelatin support. These data are confirmed by adding TIMP-1 and TIMP-2 to young cells which reproduces aged AoSMCs migratory behavior. The opposite effect was obtained in young cells silencing MMP-2 and TIMP-2.
Vigetti
Davide
D
Department of Experimental Biomedical and Clinical Sciences, University of Insubria, Varese, Italy.
Moretto
Paola
P
Viola
Manuela
M
Genasetti
Anna
A
Rizzi
Manuela
M
Karousou
Evgenia
E
Clerici
Moira
M
Bartolini
Barbara
B
Pallotti
Francesco
F
De Luca
Giancarlo
G
Passi
Alberto
A
D000818:Animals; D001011:Aorta; D002465:Cell Movement; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000502:physiology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D018960:Hyaluronan Receptors; D019714:Tissue Inhibitor of Metalloproteinases; D006820:Hyaluronic Acid; D020778:Matrix Metalloproteinase 2