This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 97/5/427    most recent 01.RES.0000179776.40216.a9v1 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 Kaplan-Albuquerque, N. Articles by Nemenoff, R. A. Search for Related Content PubMed PubMed Citation Articles by Kaplan-Albuquerque, N. Articles by Nemenoff, R. A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Related Collections Smooth muscle proliferation and differentiation Related Article

(Circulation Research. 2005;97:427.)
© 2005 American Heart Association, Inc.

Molecular Medicine

Depletion of Serum Response Factor by RNA Interference Mimics the Mitogenic Effects of Platelet Derived Growth Factor-BB in Vascular Smooth Muscle Cells

Nihal Kaplan-Albuquerque, Vicki Van Putten, Mary C. Weiser-Evans, Raphael A. Nemenoff

From the Department of Medicine, University of Colorado Health Sciences Center, Denver.

Correspondence to Dr Raphael A. Nemenoff, Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Health Sciences Center, Box C-281, 4200 E 9th Ave, Denver, CO 80262. E-mail Raphael.Nemenoff{at}UCHSC.edu

Promoters of many smooth muscle-specific genes (SM-genes) contain multiple CArG boxes, which represent a binding site for serum response factor (SRF). Transciptional control through these regions involves interactions with SRF and specific coactivators such as myocardin. We have previously reported that suppression of SM-gene expression by platelet derived growth factor (PDGF) is associated with redistribution of SRF, leading to lower intra-nuclear levels, and a reduction in SRF transactivation. To further assess the role of SRF depletion on VSMC phenotype, the current study used RNA interference (RNAi). Two SRF-specific sequences constructed as hairpins were stably expressed in rat VSMC. Clones expressing SRF RNAi had no detectable SRF expression by immunoblotting, and showed diminished levels of SM -actin protein and promoter activity. Unexpectedly, depletion of VSMC resulted in increased rates of proliferation and migration. Several genes whose expression is increased by PDGF stimulation, including c-Jun, were similarly induced in cells lacking SRF. Effects of SRF depletion were not attributable to altered PDGF receptor activity or alterations in activation of Akt. These data indicate that loss of SRF transactivation in VSMC, in this case through suppression via RNAi, induces biological responses similar to that seen with PDGF.

Key Words: vascular smooth muscle cells • serum response factor • RNA interference • platelet derived growth factor

Related Article:

SRF Function in Vascular Smooth Muscle: When Less is More?

Blanca Camoretti-Mercado, Nickolai O. Dulin, and Julian Solway
Circ. Res. 2005 97: 409-410. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				R.-W. Guo, H. Wang, P. Gao, M.-Q. Li, C.-Y. Zeng, Y. Yu, J.-F. Chen, M.-B. Song, Y.-K. Shi, and L. Huang An essential role for stromal interaction molecule 1 in neointima formation following arterial injury Cardiovasc Res, March 1, 2009; 81(4): 660 - 668. [Abstract] [Full Text] [PDF]

				H. Lin, J. McGrath, P. Wang, and T. Lee Cellular Toxicity Induced by SRF-Mediated Transcriptional Squelching Toxicol. Sci., March 1, 2007; 96(1): 83 - 91. [Abstract] [Full Text] [PDF]

				J. M. Miano, X. Long, and K. Fujiwara Serum response factor: master regulator of the actin cytoskeleton and contractile apparatus Am J Physiol Cell Physiol, January 1, 2007; 292(1): C70 - C81. [Abstract] [Full Text] [PDF]

				G.C. T. Pipes, E. E. Creemers, and E. N. Olson The myocardin family of transcriptional coactivators: versatile regulators of cell growth, migration, and myogenesis. Genes & Dev., June 15, 2006; 20(12): 1545 - 1556. [Abstract] [Full Text] [PDF]

				B. Camoretti-Mercado, N. O. Dulin, and J. Solway SRF Function in Vascular Smooth Muscle: When Less is More? Circ. Res., September 2, 2005; 97(5): 409 - 410. [Full Text] [PDF]