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Hic-5 Mediates TGFβ-Induced Adhesion in Vascular Smooth Muscle Cells by a Nox4-Dependent Mechanism

Isabel Fernandez1, Abel Martin-Garrido1, Dennis W Zhou1

  • 1From the Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (I.F., A.M.-G., R.E.C., B.S.-R., A.V., B.L., K.K.G., A.S.M.); and Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta (D.W.Z., A.J.G.).

Arteriosclerosis, Thrombosis, and Vascular Biology
|March 28, 2015
PubMed
Abstract

Insights

Transforming growth factor beta (TGFβ) stimulates vascular smooth muscle cell migration and adhesion by activating Nox4, which induces Hic-5 and Hsp27 to regulate focal adhesions.

Area of Science:

  • Cell biology
  • Biochemistry
  • Vascular biology

Background:

  • Focal adhesions (FAs) are crucial for vascular smooth muscle cell (VSMC) functions like migration.
  • Nox4, a hydrogen peroxide (H2O2)-producing enzyme, influences FA number in VSMCs.
  • Downstream effectors of Nox4 in FA regulation remain unidentified.

Purpose of the Study:

  • To investigate the roles of Hic-5 and Hsp27 in TGFβ-induced, Nox4-mediated VSMC adhesion and migration.
  • To elucidate the mechanism linking Nox4, Hic-5, and Hsp27 in VSMC focal adhesion regulation.

Main Methods:

  • Molecular biology techniques
  • Biochemistry techniques
  • Analysis of gene expression and protein interactions
  • Cellular assays for adhesion and migration

Main Results:

  • TGFβ, via Nox4, upregulates Hic-5 and Hsp27 expression and interaction, facilitating Hic-5 localization to FAs.
  • Hic-5 is essential for TGFβ-induced increases in FA number, adhesion forces, and VSMC migration.
  • Nox4 downregulation impairs TGFβ-induced Smad signaling; TGFβ-mediated Hic-5 and Hsp27 upregulation is blocked in Smad4-deficient cells.

Conclusions:

  • Hic-5 and Hsp27 act as downstream effectors of Nox4.
  • These proteins are required for TGFβ-stimulated FA formation, adhesion strength, and migration in VSMCs.
Keywords:
Hic5 proteinHsp27 proteinNox4 proteincell migration assayfocal adhesionsvascular smooth muscle

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