The Four-and-a-half LIM Domain Protein 2 Regulates Vascular Smooth Muscle Phenotype and Vascular Tone

Authors

• Nicole A. Neuman
• Susan Ma
• Gavin R. Schnitzler
• Yan Zhu

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.

Comments

This is an Open Access article under the CC BY license.

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