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- Kate M. Herum
- Department of Bioengineering, University of California San Diego, La Jolla, CA 92093
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- Jonas Choppe
- Department of Bioengineering, University of California San Diego, La Jolla, CA 92093
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- Aditya Kumar
- Department of Bioengineering, University of California San Diego, La Jolla, CA 92093
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- Adam J. Engler
- Department of Bioengineering, University of California San Diego, La Jolla, CA 92093
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- Andrew D. McCulloch
- Department of Bioengineering, University of California San Diego, La Jolla, CA 92093
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- Andres J. Garcia
- editor
書誌事項
- 公開日
- 2017-07-07
- DOI
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- 10.1091/mbc.e17-01-0014
- 公開者
- American Society for Cell Biology (ASCB)
この論文をさがす
説明
<jats:p> Cardiac fibrosis is a serious condition currently lacking effective treatments. It occurs as a result of cardiac fibroblast (CFB) activation and differentiation into myofibroblasts, characterized by proliferation, extracellular matrix (ECM) production and stiffening, and contraction due to the expression of smooth muscle α-actin. The mechanical properties of myocardium change regionally and over time after myocardial infarction (MI). Although mechanical cues are known to activate CFBs, it is unclear which specific mechanical stimuli regulate which specific phenotypic trait; thus we investigated these relationships using three in vitro models of CFB mechanical activation and found that 1) paracrine signaling from stretched cardiomyocytes induces CFB proliferation under mechanical conditions similar to those of the infarct border region; 2) direct stretch of CFBs mimicking the mechanical environment of the infarct region induces a synthetic phenotype with elevated ECM production; and 3) progressive matrix stiffening, modeling the mechanical effects of infarct scar maturation, causes smooth muscle α-actin fiber formation, up-regulation of collagen I, and down-regulation of collagen III. These findings suggest that myocyte stretch, fibroblast stretch, and matrix stiffening following MI may separately regulate different profibrotic traits of activated CFBs. </jats:p>
収録刊行物
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- Molecular Biology of the Cell
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Molecular Biology of the Cell 28 (14), 1871-1882, 2017-07-07
American Society for Cell Biology (ASCB)