The serpin protease nexin-1 regulates vascular smooth muscle cell adhesion, spreading, migration and response to thrombin.
BACKGROUND
Protease nexin-1 (PN-1) is an important physiological regulator of thrombin in the brain. PN-1 is also present in aortic smooth muscle cells and may thus participate in vascular biology. However, little is known about its function in the vessel wall.


OBJECTIVE
In this study, we investigated the effect of PN-1 overexpression in smooth muscle cells (SMCs), on their sensitivity to thrombin, and their capacity for adhesion, spreading and migration.


RESULTS
Two clones exhibiting a two- to threefold increase in PN-1 expression were selected and compared with untransfected and mock-transfected cells. Overexpression of PN-1 was observed to inhibit thrombin-induced cell responses as indicated by a twofold decrease in induction of PAI-1 expression, a decreased calcium mobilization in response to low thrombin concentrations and a twofold increase in the capacity to inhibit thrombin catalytic activity. Overexpression of PN-1 did not modify adhesion, spreading, and migration of SMCs on type I collagen. In contrast, SMCs overexpressing PN-1 exhibited a 40% reduction in adhesion, a 50% reduction in spreading and a complete absence of migration on vitronectin when compared with control SMCs.


CONCLUSIONS
Our studies thus reveal that PN-1 is likely to play a critical role in regulating essential cell functions such as (i) thrombin-induced responses, which are dependent on its antiprotease activity, and (ii) adhesion, spreading, and migration, which are independent of its antiprotease activity and may be related to its interaction with other partners, such as vitronectin in the present case.
Richard
B
B
INSERM U698, CHU X. Bichat, France.
Pichon
S
S
Arocas
V
V
Venisse
L
L
Berrou
E
E
Bryckaert
M
M
Jandrot-Perrus
M
M
Bouton
M-C
MC
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D058255:Protease Nexins; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D014162:Transfection; D019096:Vitronectin / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D018076:DNA, Complementary; D017395:Plasminogen Activator Inhibitor 1; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D019096:Vitronectin; D013917:Thrombin