title: 6A3-5/Osa2 is an early activated gene implicated in the control of vascular smooth muscle cell functions.
abstract: Vascular smooth muscle cells (VSMC) growth plays a key role in the pathophysiology of vascular diseases. However, the molecular mechanisms controlling gene transcription in VSMC remain poorly understood. We previously identified, by differential display, a new gene (6A3-5) overexpressed in proliferating rat VSMC. In this study, we have cloned the full-length cDNA by screening a rat foetal brain cDNA library and investigated its functions. The 6A3-5 protein shows 4 putative conserved functional motifs: a DNA binding domain called ARID (AT-rich interaction domain), two recently described motifs (Osa Homology Domain), and a nuclear localization signal. The deduced protein sequence was observed to be 85% identical to the recently described human Osa2 gene. Immunolabelling, using an anti-6A3-5/Osa2 monoclonal antibody, showed a nuclear localization of the 6A3-5/Osa2 protein. In addition, PDGF upregulated 6A3-5/Osa2 expression at both the transcript and protein levels in a dose and time-dependent fashion. The pattern of upregulation by PDGF was reminiscent of the early responsive gene c-fos. The PDGF-induced upregulation of 6A3-5/Osa2 and proliferation of VSMC were significantly inhibited in a dose and sequence-dependent fashion by an antisense, but not by sense, scrambled or mismatched oligonucleotides directed against 6A3-5/Osa2. In VSMC of aortas derived from hypertensive (LH) rats, 6A3-5/Osa2 is overexpressed as compared to that in normotensive (LL) rats. The 6A3-5/Osa2-gene expression is downregulated by an ACE inhibitor and upregulated by exogenous AngiotensinII in LH rats. In summary, these results indicate that 6A3-5/Osa2 is an early activated gene that belongs to a new family of proteins involved in the control of VSMC growth.
authors.affiliation: INSERM XR331, Faculté of Médicine Laënnec, Lyon 69372, France.|Genomics and Atherothrombosis, Thrombosis Research Institute, London SW3 6LR, UK.
authors.forename: Gwenaele
authors.initials: G
authors.lastname: Garin
authors.affiliation: INSERM XR331, Faculté of Médicine Laënnec, Lyon 69372, France.|Genomics and Atherothrombosis, Thrombosis Research Institute, London SW3 6LR, UK.
authors.forename: Kazem
authors.initials: K
authors.lastname: Zibara
authors.affiliation: Département de Physiologie et Pharmacologie Clinique, Faculté de Pharmacie, Université Lyon 1, Lyon, France.
authors.forename: Frederick
authors.initials: F
authors.lastname: Aguilar
authors.affiliation: Département de Physiologie et Pharmacologie Clinique, Faculté de Pharmacie, Université Lyon 1, Lyon, France.
authors.forename: Ming
authors.initials: M
authors.lastname: Lo
authors.affiliation: Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht, The Netherlands.
authors.forename: Adam
authors.initials: A
authors.lastname: Hurlstone
authors.affiliation: Center for Cardiovascular Biology and Medicine, King's College, University of London, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Poston
authors.affiliation: INSERM XR331, Faculté of Médicine Laënnec, Lyon 69372, France.|Genomics and Atherothrombosis, Thrombosis Research Institute, London SW3 6LR, UK.|Center for Cardiovascular Biology and Medicine, King's College, University of London, UK.
authors.forename: John L
authors.initials: JL
authors.lastname: Mcgregor