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Related Experiment Videos

Thymosin beta4 regulation, expression and function in aortic valve interstitial cells.

Quan-Yi Li1, Peter L Jones, Robert P Lafferty

  • 1Division of Cardiology, Abramson Pediatric Research Center, The Children's Hospital of Philadelphia, PA 19104, USA.

The Journal of Heart Valve Disease
|October 3, 2002
PubMed
Summary

Tenascin-C up-regulates thymosin beta-4 in aortic valve cells, potentially initiating valvular calcification. This extracellular matrix protein is linked to mineralization and matrix metalloproteinase-2 (MMP-2) activity.

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Area of Science:

  • Cardiovascular Biology
  • Extracellular Matrix Research
  • Cellular Signaling

Background:

  • Tenascin-C, an extracellular matrix protein, is present in calcified aortic valves and associated with matrix metalloproteinase (MMP)-2.
  • Tenascin-C is absent in non-calcified human aortic valves.

Purpose of the Study:

  • To identify downstream targets of tenascin-C in aortic valve interstitial cells.

Main Methods:

  • Subtractive hybridization was employed using sheep aortic valve interstitial cells (SAVIC) cultured on collagen with or without tenascin-C.
  • Cell culture studies assessed thymosin beta-4 production and its effects on SAVIC.

Main Results:

  • Subtractive hybridization identified thymosin beta-4, an actin-binding protein, in nearly 70% of isolated clones.

Related Experiment Videos

  • Tenascin-C up-regulated thymosin beta-4 expression in SAVIC.
  • Thymosin beta-4 induced F-actin re-orientation and MMP-2 in SAVIC, though antisense oligonucleotides did not suppress MMP-2.
  • Conclusions:

    • Thymosin beta-4 is up-regulated by tenascin-C in aortic valve interstitial cells.
    • Thymosin beta-4 may play a role in the initial stages of valvular calcification.