6A3-5/Osa2 is an Early Activated Gene Implicated in the Control of Vascular Smooth Muscle Cell Functions

Garin, Gwenaele; Zibara, Kazem; Aguilar, Frederick; Lo, Ming; Hurlstone, Adam; Poston, Robin; Mcgregor, John L.

doi:https://doi.org/10.1155/JBB/2006/97287

BioMed Research International

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Research Article | Open Access

Volume 2006 | Article ID 097287 | https://doi.org/10.1155/JBB/2006/97287

6A3-5/Osa2 is an Early Activated Gene Implicated in the Control of Vascular Smooth Muscle Cell Functions

Gwenaele Garin,^1,2Kazem Zibara,^1,2Frederick Aguilar,³Ming Lo,³Adam Hurlstone,⁴Robin Poston,⁵and John L. Mcgregor^1,2,5

Received17 Apr 2006

Revised11 Jul 2006

Accepted17 Jul 2006

Published11 Oct 2006

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.

References

R Ross, “The pathogenesis of atherosclerosis: a perspective for the 1990s,” Nature, vol. 362, no. 6423, pp. 801–809, 1993.
View at: Publisher Site | Google Scholar
S M Schwartz, G R Campbell, and J H Campbell, “Replication of smooth muscle cells in vascular disease,” Circulation Research, vol. 58, no. 4, pp. 427–444, 1986.
View at: Google Scholar
A D Hughes, G F Clunn, J Refson, and C Demoliou-Mason, “Platelet-derived growth factor (PDGF): actions and mechanisms in vascular smooth muscle,” General Pharmacology, vol. 27, no. 7, pp. 1079–1089, 1996.
View at: Publisher Site | Google Scholar
M J Daemen, D M Lombardi, F T Bosman, and S M Schwartz, “Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall,” Circulation Research, vol. 68, no. 2, pp. 450–456, 1991.
View at: Google Scholar
R M Touyz, “The role of angiotensin II in regulating vascular structural and functional changes in hypertension,” Current Hypertension Reports, vol. 5, no. 2, pp. 155–164, 2003.
View at: Google Scholar
R V Sharma and R C Bhalla, “PDGF-induced mitogenic signaling is not mediated through protein kinase C and c-fos pathway in VSM cells,” American Journal of Physiology, vol. 264, no. 1 pt 1, pp. C71–C79, 1993.
View at: Google Scholar
A Hultgardh-Nilsson, B Cercek, J-W Wang et al., “Regulated expression of the Ets-1 transcription factor in vascular smooth muscle cells in vivo and in vitro,” Circulation Research, vol. 78, no. 4, pp. 589–595, 1996.
View at: Google Scholar
K Brand, S Page, G Rogler et al., “Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion,” Journal of Clinical Investigation, vol. 97, no. 7, pp. 1715–1722, 1996.
View at: Google Scholar
K K Griendling and R W Alexander, “Cellular mechanisms of angiotensin II action,” in Textbook of Hypertension, J D Swales, Ed., pp. 244–253, Blackwell, Oxford, UK, 1994.
View at: Google Scholar
K Zibara, G Garin, and J L McGregor, “Identification, structural, and functional characterization of a new early gene (6A3-5,7 kb): implication in the proliferation and differentiation of smooth muscle cells,” Journal of Biomedicine and Biotechnology, vol. 2005, no. 3, pp. 254–270, 2005.
View at: Publisher Site | Google Scholar
D Wilsker, A Patsialou, P B Dallas, and E Moran, “ARID proteins: a diverse family of DNA binding proteins implicated in the control of cell growth, differentiation, and development,” Cell Growth and Differentiation, vol. 13, no. 3, pp. 95–106, 2002.
View at: Google Scholar
S L Gregory, R D Kortschak, B Kalionis, and R Saint, “Characterization of the dead ringer gene identifies a novel, highly conserved family of sequence-specific DNA-binding proteins,” Molecular and Cellular Biology, vol. 16, no. 3, pp. 792–799, 1996.
View at: Google Scholar
J H Campbell and G R Campbell, “Phenotypic modulation of smooth muscle cells in primary culture,” in Vascular Smooth Muscle in Culture, J H Campbell and G R Campbell, Eds., CRC Press, Boca Raton, Fla, 1st edition, 1987.
View at: Google Scholar
A Hurlstone, I A Olave, N Barker, M Van Noort, and H Clevers, “Cloning and characterization of hELD/0SA1, a novel BRG1 interacting protein,” Biochemical Journal, vol. 364, no. 1, pp. 255–264, 2002.
View at: Google Scholar
G Garin, C Badid, B McGregor et al., “Ischemia induces early expression of a new transcription factor (6A3-5) kidney vascular smooth muscle cells: studies in rat and human renal pathology,” American Journal of Pathology, vol. 163, no. 6, pp. 2485–2494, 2003.
View at: Google Scholar
F Aguilar, M Lo, B Claustrat, J M Saez, J Sassard, and J Y Li, “Hypersensitivity of the adrenal cortex to trophic and secretory effects of angiotensin II in Lyon genetically-hypertensive rats,” Hypertension, vol. 43, no. 1, pp. 87–93, 2004.
View at: Publisher Site | Google Scholar
Z Kozmik, O Machoň, J Králová, J Krešlová, J Pačes, and C Vlček, “Characterization of mammalian orthologues of the Drosophila osa gene: cDNA cloning, expression, chromosomal localization, and direct physical interaction with brahma chromatin-remodeling complex,” Genomics, vol. 73, no. 2, pp. 140–148, 2001.
View at: Publisher Site | Google Scholar
J E Treisman, A Luk, G M Rubin, and U Heberlein, “Eyelid antagonizes wingless signaling during Drosophila development and has homology to the bright family of DNA-binding proteins,” Genes and Development, vol. 11, no. 15, pp. 1949–1962, 1997.
View at: Google Scholar
C L Peterson and I Herskowitz, “Characterization of the yeast SWI1, SWI2, and SWI3 genes, which encode a global activator of transcription,” Cell, vol. 68, no. 3, pp. 573–583, 1992.
View at: Publisher Site | Google Scholar
S L Gregory, R D Kortschak, B Kalionis, and R Saint, “Characterization of the dead ringer gene identifies a novel, highly conserved family of sequence-specific DNA-binding proteins,” Molecular and Cellular Biology, vol. 16, no. 3, pp. 792–799, 1996.
View at: Google Scholar
C F Webb, “The transcription factor, Bright and immunoglobulin heavy chain expression,” Immunologic Research, vol. 24, no. 2, pp. 149–161, 2001.
View at: Publisher Site | Google Scholar
M Watanabe, M D Layne, C-M Hsieh et al., “Regulation of smooth muscle cell differentiation by AT-rich interaction domain transcription factors Mrf2 $a$ and Mrf2 $ß$ ,” Circulation Research, vol. 91, no. 5, pp. 382–389, 2002.
View at: Publisher Site | Google Scholar
C M Shanahan and P L Weissberg, “Smooth muscle cell heterogeneity: patterns of gene expression in vascular smooth muscle cells in vitro and in vivo,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 18, no. 3, pp. 333–338, 1998.
View at: Google Scholar
N Blaes, M C Bourdillon, J M Daniel-Lamaziere, J J Michaille, M Andujar, and C Covacho, “Isolation of two morphologically distinct cell lines from rat arterial smooth muscle expressing high tumorigenic potentials,” In Vitro Cellular & Developmental Biology, vol. 27, no. 9, pp. 725–734, 1991.
View at: Google Scholar
H Inoue, T Furukawa, S Giannakopoulos, S Zhou, D S King, and N Tanese, “Largest subunits of the human SWI/SNF chromatin-remodeling complex promote transcriptional activation by steroid hormone receptors,” Journal of Biological Chemistry, vol. 277, no. 44, pp. 41674–41685, 2002.
View at: Publisher Site | Google Scholar
E Van Belle, C Bauters, N Wernert et al., “Angiotensin converting enzyme inhibition prevents proto-oncogene expression in the vascular wall after injury,” Journal of Hypertension, vol. 13, no. 1, pp. 105–112, 1995.
View at: Google Scholar
D A Linseman, C W Benjamin, and D A Jones, “Convergence of angiotensin II and platelet-derived growth factor receptor signaling cascades in vascular smooth muscle cells,” Journal of Biological Chemistry, vol. 270, no. 21, pp. 12563–12568, 1995.
View at: Publisher Site | Google Scholar
S Kim, Y Zhan, Y Izumi, H Yasumoto, M Yano, and H Iwao, “In vivo activation of rat aortic platelet-derived growth factor and epidermal growth factor receptors by angiotensin II and hypertension,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 20, no. 12, pp. 2539–2545, 2000.
View at: Google Scholar
M Vincent and J Sassard, “Lyon strains,” in Textbook of Hypertension, J D Swales, Ed., pp. 455–456, Blackwell, Oxford, UK, 1994.
View at: Google Scholar
P Lantelme, M Lo, L Luttenauer, and J Sassard, “Pivotal role of the renin-angiotensin system in Lyon hypertensive rats,” American Journal of Physiology, vol. 273, no. 5 pt 2, pp. R1793–R1799, 1997.
View at: Google Scholar
F C Tanner, H Greutert, C Barandier, K Frischknecht, and T F Lüscher, “Different cell cycle regulation of vascular smooth muscle in genetic hypertension,” Hypertension, vol. 42, no. 2, pp. 184–188, 2003.
View at: Publisher Site | Google Scholar
A Sabri, B I Levy, P Poitevin et al., “Differential roles of ${AT}_{1}$ and ${AT}_{2}$ receptor subtypes in vascular trophic and phenotypic changes in response to stimulation with angiotensin II,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 17, no. 2, pp. 257–264, 1997.
View at: Google Scholar
N Kaplan-Albuquerque, C Garat, C Desseva, P L Jones, and R A Nemenoff, “Platelet-derived growth factor-BB-mediated activation of Akt suppresses smooth muscle-specific gene expression through inhibition of mitogen-activated protein kinase and redistribution of serum response factor,” Journal of Biological Chemistry, vol. 278, no. 41, pp. 39830–39838, 2003.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2006 Gwenaele Garin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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