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Mitogen-activated protein kinase 14 is a novel negative regulatory switch for the vascular smooth muscle cell

Xiaochun Long1, Sarah L Cowan, Joseph M Miano

  • 1Department of Medicine, Aab Cardiovascular Research Institute, Box CVRI, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Rochester, NY 14642, USA. xiaochun_long@urmc.rochester.edu

Arteriosclerosis, Thrombosis, and Vascular Biology
|November 24, 2012
PubMed
Abstract

Insights

Knocking down p38 mitogen-activated protein kinase alpha (MAPK14) unexpectedly boosts vascular smooth muscle cell (VSMC) differentiation markers. This suggests MAPK14 negatively regulates VSMC differentiation.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • p38 mitogen-activated protein kinase (MAPK) is known to promote vascular smooth muscle cell (VSMC) differentiation.
  • The specific role of dominant p38MAPK isoforms in this process requires further investigation.

Purpose of the Study:

  • To evaluate the effects of knocking down a dominant p38MAPK isoform on VSMC differentiation.
  • To elucidate the signaling pathways involved in p38MAPK-mediated VSMC differentiation.

Main Methods:

  • Knockdown of p38MAPKα (MAPK14) in human coronary artery SMCs.
  • Analysis of VSMC differentiation genes (e.g., miR145, ACTA2, CNN1, LMOD1, TAGLN).
  • Assessment of SRF cofactors (MYOCD, MKL1) and pathway inhibitors.
  • Immunostaining and Western blotting in injured mouse carotid arteries.

Main Results:

  • MAPK14 knockdown increased VSMC differentiation markers without significantly altering SRF and its cofactors.
  • A RhoA-MKL1-SRF-dependent pathway mediated these effects, with MAPK14 knockdown promoting MKL1 nuclear localization.
  • In injured mouse arteries, elevated MAPK14 correlated with reduced VSMC marker expression.

Conclusions:

  • Reduced MAPK14 expression unexpectedly increases VSMC contractile gene expression.
  • MAPK14 signaling appears to play an unrecognized negative regulatory role in VSMC differentiation.

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