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Updated: May 12, 2026

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
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Spry1 and Spry4 differentially regulate human aortic smooth muscle cell phenotype via Akt/FoxO/myocardin signaling

Xuehui Yang1, Yan Gong, Yuefeng Tang

  • 1Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine, USA. yangx@mmc.org

Plos One
|April 5, 2013
PubMed
Abstract

Insights

Spry1 protein is crucial for maintaining vascular smooth muscle cell (VSMC) differentiation by activating the Akt pathway. Spry4 protein has opposing effects, suppressing VSMC differentiation.

Area of Science:

  • Vascular Biology
  • Cell Signaling
  • Molecular Medicine

Background:

  • Vascular smooth muscle cell (VSMC) phenotype changes in diseases like restenosis and atherosclerosis.
  • Cytokines and receptor tyrosine kinases (RTK) pathways (MAPK/ERK, PI3K/Akt) regulate VSMC phenotype.
  • Spry proteins are feedback regulators of RTK signaling, but their role in VSMC is unknown.

Purpose of the Study:

  • To investigate the role of Spry proteins in maintaining the differentiated state of human VSMC.
  • To elucidate the signaling pathways involved in Spry-mediated VSMC phenotype modulation.

Main Methods:

  • siRNA knockdown to assess Spry1 and Spry4 function.
  • Chromatin immunoprecipitation (ChIP) assays to study transcription factor binding.
  • Analysis of Akt and MAPK/ERK signaling pathways.
  • Measurement of VSMC differentiation markers and myocardin mRNA levels.

Main Results:

  • Spry1 is essential for maintaining human VSMC differentiation in vitro.
  • Spry1 enhances Akt activation and VSMC marker expression, with minimal effect on MAPK/ERK.
  • ERK signaling negatively impacts Akt activation and VSMC differentiation.
  • Spry4 antagonizes both Akt and MAPK/ERK signaling, suppressing VSMC differentiation.
  • Spry1 increases and Spry4 decreases myocardin mRNA levels via an Akt/FoxO pathway.

Conclusions:

  • Spry1 and Spry4 exhibit opposing roles in VSMC phenotypic modulation.
  • Spry1 maintains VSMC differentiation through an Akt/FoxO/myocardin pathway.
  • These findings offer insights into therapeutic strategies for vascular diseases.

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