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| Status |
Public on Jun 02, 2021 |
| Title |
Transthyretin alters cardiac fibroblast structure, function and inflammatory gene expression. |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Age-related wild type transthyretin amyloidosis (wtATTR) is characterized by systemic deposition of amyloidogenic fibrils of misfolded transthyretin (TTR) in the connective tissue of many organs. In the heart this leads to cardiac dysfunction, which is a significant cause of age-related heart failure. The hypothesis tested is that TTR affects cardiac fibroblasts in ways that may contribute to fibrosis. When primary cardiac fibroblasts were cultured on TTR-deposited substrates, the F-actin cytoskeleton disorganized, focal adhesion formation decreased, and nuclear shape was flattened. Fibroblasts had faster collective and single cell migration velocities on TTR-deposited substrates. Additionally, fibroblasts cultured on microposts with TTR deposition had reduced attachment and increased proliferation above untreated. Transcriptomic and proteomic analyses of fibroblasts grown on glass covered with TTR showed significant upregulation of inflammatory genes after 48 hours, indicative of progression in TTR-based diseases. Together, results suggest that TTR deposited in tissue extracellular matrix may affect both the structure, function and gene expression of cardiac fibroblasts. As therapies for wtATTR are cost-prohibitive and only slow disease progression, better understanding of cellular maladaptation may elucidate novel therapeutic targets.
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| Overall design |
Three samples of cardiac fibroblasts grown on both untreated (UT) and TTR fibril-containing (TTR) substrates.
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| Contributor(s) |
Dittloff KT, Iezzi A, Zhong JX, Mohindra P, Desai TA, Russell B |
| Citation(s) |
34018852 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| P01 HL062426 |
Integrated Mechanisms of Cardiac Maladaptation |
BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS |
R John Solaro |
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| |
| Submission date |
Jun 01, 2021 |
| Last update date |
Sep 01, 2021 |
| Contact name |
Brenda Russell |
| E-mail(s) |
russell@uic.edu
|
| Phone |
3124130407
|
| Organization name |
University Illinois at Chicago
|
| Department |
Physiology
|
| Street address |
835 S Wolcott Ave
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60612 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL25947 |
Illumina NovaSeq 6000 (Rattus norvegicus) |
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| Samples (6)
|
| GSM5351198 |
Neonatal Rat Cardiac Fibroblast - control rep 1 |
| GSM5351199 |
Neonatal Rat Cardiac Fibroblast - control rep 2 |
| GSM5351200 |
Neonatal Rat Cardiac Fibroblast - control rep 3 |
| GSM5351201 |
Neonatal Rat Cardiac Fibroblast - Treatment rep 1 |
| GSM5351202 |
Neonatal Rat Cardiac Fibroblast - Treatment rep 2 |
| GSM5351203 |
Neonatal Rat Cardiac Fibroblast - Treatment rep 3 |
|
| Relations |
| BioProject |
PRJNA734300 |
| SRA |
SRP322153 |
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