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| Status |
Public on Jun 04, 2020 |
| Title |
Type V collagen in scar tissue regulates the size of scar after heart injury |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The mammalian heart possesses a poor ability to regenerate after acute ischemic cardiac injury and lost cardiac muscle is replaced by scar tissue. Multiple clinical studies demonstrate that the size of scar tissue following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors that regulate the size of scar after ischemic cardiac injury. In this report, we demonstrate that collagen V, a fibrillar collagen and a minor constituent of heart scars regulates the size of heart scars after ischemic cardiac injury. Depletion of collagen V in heart scars in two independent animal models led to a significant and paradoxical increase in post infarction scar tissue size with worsening of heart function. A systems genetics approach analyzing genes versus traits across 100 in-bred strains of mice independently demonstrated that collagen V is a critical driver of post injury heart function. We show that collagen V deficiency alters the ultra-structure and mechanical properties of scar tissue that make it more vulnerable to expansion. There is altered reciprocal feedback between matrix and cells that induce expression of specific mechanosensitive integrins which drive fibroblast activation and increased ECM gene expression. Scar size increases. Administration of cilengitide, an inhibitor of specific integrins, completely rescues the phenotype of increased post injury scarring, myofibroblast formation and cardiac dysfunction in collagen V deficient mice. These observations demonstrate that collagen V, a structural constituent of heart scar tissue regulates scar size in an integrin dependent manner.
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| Overall design |
Examination of mouse heart cell expression changes after Col5a1 knock out and treatment with cilengitide
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| |
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| Contributor(s) |
Ma F, Yokota T, Deb A, Pellegrini M |
| Citation(s) |
32621799 |
| |
| Submission date |
Jun 03, 2020 |
| Last update date |
Sep 03, 2020 |
| Contact name |
Feiyang Ma |
| Organization name |
UCLA
|
| Department |
Molecular Biology Institute
|
| Lab |
Pellegrini Lab
|
| Street address |
610, Charles Young Dr East, TLSB 3000C
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (4)
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| Relations |
| BioProject |
PRJNA636977 |
| SRA |
SRP265775 |
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