Angiotensin II modulates frizzled-2 receptor expression in rat vascular smooth muscle cells.
Ang II (angiotensin II) has multiple effects on vascular smooth muscle cells through the modulation of different classes of genes. Using the mRNA differential-display method to investigate gene expression in rat aortic smooth muscle cells in culture in response to 3 h of Ang II stimulation, we observed that Ang II down-regulated the expression of a member of the family of transmembrane receptors for Wnt proteins that was identified as Fzd2 [Fzd (frizzled)-2 receptor]. Fzds are a class of highly conserved genes playing a fundamental role in the developmental processes. In vitro, time course experiments demonstrated that Ang II induced a significant increase (P<0.05) in Fzd2 expression after 30 min, whereas it caused a significant decrease (P<0.05) in Fzd2 expression at 3 h. A similar rapid up-regulation after Ang II stimulation for 30 min was evident for TGFbeta1 (transforming growth factor beta1; P<0.05). To investigate whether Ang II also modulated Fzd2 expression in vivo, exogenous Ang II was administered to Sprague-Dawley rats (200 ng.kg(-1) of body weight.min(-1); subcutaneously) for 1 and 4 weeks. Control rats received normal saline. After treatment, systolic blood pressure was significantly higher (P<0.01), whereas plasma renin activity was suppressed (P<0.01) in Ang II- compared with the saline-treated rats. Ang II administration for 1 week did not modify Fzd2 expression in aorta of Ang II-treated rats, whereas Ang II administration for 4 weeks increased Fzd2 mRNA expression (P<0.05) in the tunica media of the aorta, resulting in a positive immunostaining for fibronectin at this time point. In conclusion, our data demonstrate that Ang II modulates Fzd2 expression in aortic smooth muscle cells both in vitro and in vivo.
Castoldi
Giovanna
G
Clinica Nefrologica, Dipartimento di Medicina Clinica, Prevenzione e Biotecnologie Sanitarie, Università degli Studi di Milano-Bicocca, Azienda Ospedaliera S. Gerardo di Monza, Via Donizetti 106, 20052 Monza, Italy.
Redaelli
Serena
S
van de Greef
Willy M M
WM
di Gioia
Cira R T
CR
Busca
Giuseppe
G
Sperti
Giovanni
G
Stella
Andrea
A
D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D001483:Base Sequence; D002478:Cells, Cultured; D029721:Drosophila Proteins; D004343:Drug Implants; D051157:Frizzled Receptors; D005786:Gene Expression Regulation / Q000187:drug effects*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000235:genetics* / Q000378:metabolism; D012083:Renin / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics; D051153:Wnt Proteins
D029721:Drosophila Proteins; D004343:Drug Implants; D051157:Frizzled Receptors; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; C101703:fz2 protein, Drosophila; D000804:Angiotensin II; C078604:Fzd2 protein, rat; D000803:Angiotensin I; D012083:Renin