Angiotensin II AT(2) receptor inhibits smooth muscle cell migration via fibronectin cell production and binding.
To explore the vascular function of the angiotensin II (ANG II) AT(2) receptor subtype (AT(2)R), we generated a vascular smooth muscle cell (SMC) line expressing the AT(2)R (SMC-vAT(2)). The involvement of AT(2)R in the motility response of SMCs was examined in SMC-vAT(2) cells and their controls (SMC-v) cultured on either laminin or fibronectin matrix proteins with the agarose drop technique. All experiments were conducted in the presence of a saturating concentration of losartan to inactivate the AT(1)R subtype. Under basal conditions, both cell lines migrated outside drops, but on laminin only. Treatment with ANG II significantly inhibited the migration of SMC-vAT(2) but not SMC-v cells, and this effect was prevented by the AT(2)R antagonist CGP-42112A. The decreased migration of SMC-vAT(2) was not associated with changes in cell growth, cytoskeleton stiffness, or smooth muscle actin, desmin, and tenascin expression. However, it was correlated with increased synthesis and binding of fibronectin. Both responses were prevented by incubation with selective AT(2)R antagonists. Addition of GRGDTP peptide, which prevents cell attachment of fibronectin, reversed the AT(2)R inhibitory effect on SMC-vAT(2) migration. These results suggest that activated ANG II AT(2)R inhibits SMC migration via cellular fibronectin synthesis and associated cell binding.
Chassagne
Catherine
C
Institut National de la Santé et de la Recherche Médicale (INSERM) U127, Hôpital Lariboisière, Université Denis Diderot, 41 boulevard de la Chapelle, 75475 Paris Cedex 10, France. catherine.chassagne@inserm.lrb.ap-hop-paris.fr
Adamy
Christophe
C
Ratajczak
Philippe
P
Gingras
Bruno
B
Teiger
Emmanuel
E
Planus
Emmanuelle
E
Oliviero
Patricia
P
Rappaport
Lydie
L
Samuel
Jane-Lise
JL
Meloche
Sylvain
S
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006801:Humans; D007457:Iodine Radioisotopes; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007457:Iodine Radioisotopes; D007797:Laminin; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin