Document Type
Article
Publication Date
5-2009
Publisher
Elsevier
Abstract
In responsetovascular injury, differentiated vascular smooth muscle cells (vSMCs) undergo a uniqueprocess knownas“phenotype modulation,” transitioning from a quiescent, “contractile” phenotype to a proliferative, “synthetic” state. We have demonstrated previously that the signaling pathway of bone morphogenetic proteins, members of the transforming growth factor family, play a role in the induction and maintenance of a contractile phenotype in human primary pulmonary artery smooth muscle cells. In this study, we show that a four-and-ahalf LIM domainprotein 2(FHL2)inhibits transcriptional activation ofvSMC-specificgenesmediatedbythebonemorphogenetic protein signaling pathway through the CArG box-binding proteins, such as serum response factor and members of the myocardin (Myocd) family. Interestingly, FHL2 does not affect recruitment of serum response factor or Myocd, however, it inhibits recruitmentofacomponentoftheSWI/SNFchromatin remodeling complex, Brg1, and RNA polymerase II, which are essential forthetranscriptionalactivation.Thisisanovelmechanism of regulation of SMC-specific contractile genes by FHL2. Finally, aortic rings from homozygous FHL2-null mice display abnormalities inbothendothelial-dependentand-independent relaxation, suggesting that FHL2 is essential for the regulation of vasomotor tone.
Recommended Citation
Neuman, N. A., Ma, S., Schnitzler, G. R., Zhu, Y., Lagna, G., & Hata, A. (2009). The Four-and-a-half LIM Domain Protein 2 Regulates Vascular Smooth Muscle Phenotype and Vascular Tone *. Journal of Biological Chemistry, 284(19), 13202–13212. https://doi.org/10.1074/jbc.M900282200
Comments
This is an Open Access article under the CC BY license.