This Article Full Text Full Text (PDF) All Versions of this Article: 91/5/382    most recent 01.RES.0000033593.05545.7Bv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Watanabe, M. Articles by Jain, M. K. Search for Related Content PubMed PubMed Citation Articles by Watanabe, M. Articles by Jain, M. K. Related Collections Gene expression Smooth muscle proliferation and differentiation

(Circulation Research. 2002;91:382.)
© 2002 American Heart Association, Inc.

Molecular Medicine

Regulation of Smooth Muscle Cell Differentiation by AT-Rich Interaction Domain Transcription Factors Mrf2 and Mrf2ß

Masafumi Watanabe, Matthew D. Layne, Chung-Ming Hsieh, Koji Maemura, Susan Gray, Mu-En Lee, Mukesh K. Jain

From the Cardiovascular (M.W., M.D.L., C.-M.H., K.M., S.G., M.-E.L., M.K.J.) and Pulmonary and Critical Care (M.D.L.) Divisions, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Mukesh K. Jain, MD, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, TH1127, Boston, MA 02115. E-mail mjain{at}rics.bwh.harvard.edu

Despite the importance of vascular smooth muscle cells in the regulation of blood vessel function, the molecular mechanisms governing their development and differentiation remain poorly understood. Using an in vitro system whereby a pluripotent neural crest cell line (MONC-1) can be induced to differentiate into smooth muscle cells, we isolated a cDNA fragment that was robustly induced during this differentiation process. Sequence analysis revealed high homology to a partial cDNA termed modulator recognition factor 2 (Mrf2). Because the full-length cDNA has not been reported, we cloned the full-length Mrf2 cDNA by cDNA library screening and 5' rapid amplification of cDNA ends and identified two isoforms of Mrf2 ( [3.0 kb] and ß [3.7 kb]) that differ in the N-terminus but share the DNA-binding domain. Protein homology analysis suggests that Mrf2 is a member of the AT-rich interaction domain family of transcription factors, which are known to be critically involved in the regulation of development and cellular differentiation. Mrf2 and Mrf2ß are highly induced during in vitro differentiation of MONC-1 cells into smooth muscle cells, and Mrf2 is expressed in adult mouse cardiac and vascular tissues. To define the function of Mrf2, we overexpressed both isoforms in 3T3 fibroblast cells and observed an induction of smooth muscle marker genes, including smooth muscle -actin and smooth muscle 22. Furthermore, Mrf2 and Mrf2ß retarded cellular proliferation. These data implicate Mrf2 as a novel regulator of smooth muscle cell differentiation and proliferation.

Key Words: smooth muscle • differentiation • proliferation • transcription factors

This article has been cited by other articles:

				M. A. Saleem, J. Zavadil, M. Bailly, K. McGee, I. R. Witherden, H. Pavenstadt, H. Hsu, J. Sanday, S. C. Satchell, R. Lennon, et al. The molecular and functional phenotype of glomerular podocytes reveals key features of contractile smooth muscle cells Am J Physiol Renal Physiol, October 1, 2008; 295(4): F959 - F970. [Abstract] [Full Text] [PDF]

				T. Yamakawa, R. H. Whitson, S.-L. Li, and K. Itakura Modulator Recognition Factor-2 Is Required for Adipogenesis in Mouse Embryo Fibroblasts and 3T3-L1 Cells Mol. Endocrinol., February 1, 2008; 22(2): 441 - 453. [Abstract] [Full Text] [PDF]

				C.-H. Wang, L.-H. Su, and C.-H. Sun A Novel ARID/Bright-like Protein Involved in Transcriptional Activation of Cyst Wall Protein 1 Gene in Giardia lamblia J. Biol. Chem., March 23, 2007; 282(12): 8905 - 8914. [Abstract] [Full Text] [PDF]

				J. M. Spin, S. Nallamshetty, R. Tabibiazar, E. A. Ashley, J. Y. King, M. Chen, P. S. Tsao, and T. Quertermous Transcriptional profiling of in vitro smooth muscle cell differentiation identifies specific patterns of gene and pathway activation Physiol Genomics, November 17, 2004; 19(3): 292 - 302. [Abstract] [Full Text] [PDF]

				G. K. Owens, M. S. Kumar, and B. R. Wamhoff Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease Physiol Rev, July 1, 2004; 84(3): 767 - 801. [Abstract] [Full Text] [PDF]

				S. Brunelli, E. Tagliafico, F. G. De Angelis, R. Tonlorenzi, S. Baesso, S. Ferrari, M. Niinobe, K. Yoshikawa, R. J. Schwartz, I. Bozzoni, et al. Msx2 and Necdin Combined Activities Are Required for Smooth Muscle Differentiation in Mesoangioblast Stem Cells Circ. Res., June 25, 2004; 94(12): 1571 - 1578. [Abstract] [Full Text] [PDF]

				J. Zhou, A. M. Hoggatt, and B. P. Herring Activation of the Smooth Muscle-specific Telokin Gene by Thyrotroph Embryonic Factor (TEF) J. Biol. Chem., April 16, 2004; 279(16): 15929 - 15937. [Abstract] [Full Text] [PDF]

				S. Li, D.-Z. Wang, Z. Wang, J. A. Richardson, and E. N. Olson The serum response factor coactivator myocardin is required for vascular smooth muscle development PNAS, August 5, 2003; 100(16): 9366 - 9370. [Abstract] [Full Text] [PDF]

				Z. Wang, D.-Z. Wang, G. C. T. Pipes, and E. N. Olson Myocardin is a master regulator of smooth muscle gene expression PNAS, June 10, 2003; 100(12): 7129 - 7134. [Abstract] [Full Text] [PDF]

				M. S. Kumar and G. K. Owens Combinatorial Control of Smooth Muscle-Specific Gene Expression Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 737 - 747. [Abstract] [Full Text] [PDF]