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Mechanical regulation of cardiac fibroblast profibrotic phenotypes
| Content Provider | Semantic Scholar |
|---|---|
| Author | Herum, Kate M. Choppe, Jonas Kumar, Aditya Engler, Adam J. McCulloch, Andrew D. |
| Copyright Year | 2017 |
| Abstract | 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. |
| Starting Page | 1871 |
| Ending Page | 1882 |
| Page Count | 12 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b7/96/1871.PMC5541838.pdf |
| Alternate Webpage(s) | https://cloudfront.escholarship.org/dist/prd/content/qt0jf3n001/qt0jf3n001.pdf?t=oqeyyh |
| PubMed reference number | 28468977 |
| Alternate Webpage(s) | https://doi.org/10.1091/mbc.E17-01-0014 |
| DOI | 10.1091/mbc.e17-01-0014 |
| Journal | Molecular biology of the cell |
| Volume Number | 28 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Activation action Cicatrix Clofibrate Collagen Diseases Down-Regulation EAF2 gene Extracellular Matrix Fibroblasts Fibrosis Muscle Cells Myocardial Infarction Myocardium Myocytes, Cardiac Myofibroblasts Paracrine Communication Phenotype Smooth muscle (tissue) Tissue fiber |
| Content Type | Text |
| Resource Type | Article |
