[Mechanisms of regulation of osteopontin expression mediated by UTP, angiotensin II and PDGF in arterial smooth muscle cells].
Osteopontin (OPN), an RGD containing extracellular matrix protein, is associated with arterial smooth muscle cells (SMC) activation in vitro and in vivo. OPN has been shown to be overexpressed in vascular injury. Its expression can be induced by many factors including growth factors, cytokines, hormones and extracellular nucleotides. We are interested in understanding mechanisms regulating the OPN mRNA steady state level in SMC. We compared the effect of two G-protein coupled receptors agonists (UTP and angiotensin II [AII]) and one tyrosin kinase receptor agonist (PDGF). We explored the effect of these three agonists both on OPN transcription using gene reporter assay and on OPN mRNA stabilisation using actinomycin D. We showed that UTP 100 microM. AII 10 microM and PDGF 50 ng/microL induced OPN transcription. Whereas UTP and AII induced a 366 +/- 81% and 338 +/- 115% activation of transcription respectively, PDGF demonstrated a lower efficiency (195 +/- 59%) inducing the transcription. Moreover, we demonstrated that UTP and AII but not PDGF were able to stabilize OPN mRNA. This effect seems to be specific to G-protein coupled receptor agonists since previous studies demonstrated that intracellular receptor agonists did not stabilise OPN mRNA. Thus, the lower increase of OPN mRNA level in response to PDGF stimulation compared to AII or UTP could be explain by both, the lower activation of the OPN promoter and the effect of UTP and AII on OPN mRNA stabilisation.
Renault
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INSERM U441, avenue du Haut-Lévêque, 33600 Pessac.
Jalvy
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Belloc
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Desgranges
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Gadeau
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D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000502:physiology*; D002448:Cell Adhesion; D016207:Cytokines; D019204:GTP-Binding Proteins; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology*; D053495:Osteopontin; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D014544:Uridine Triphosphate; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D016207:Cytokines; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D014662:Vasoconstrictor Agents; D053495:Osteopontin; D000804:Angiotensin II; D019204:GTP-Binding Proteins; D014544:Uridine Triphosphate