| Autor: |
Dominik Müller, Sören Donath, Emanuel Georg Brückner, Santoshi Biswanath Devadas, Fiene Daniel, Lara Gentemann, Robert Zweigerdt, Alexander Heisterkamp, Stefan Michael Klaus Kalies |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Bioengineering, Vol 8, Iss 12, p 213 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2306-5354 |
| DOI: |
10.3390/bioengineering8120213 |
| Popis: |
The proper function of cardiomyocytes (CMs) is highly related to the Z-disc, which has a pivotal role in orchestrating the sarcomeric cytoskeletal function. To better understand Z-disc related cardiomyopathies, novel models of Z-disc damage have to be developed. Human pluripotent stem cell (hPSC)-derived CMs can serve as an in vitro model to better understand the sarcomeric cytoskeleton. A femtosecond laser system can be applied for localized and defined damage application within cells as single Z-discs can be removed. We have investigated the changes in force generation via traction force microscopy, and in gene expression after Z-disc manipulation in hPSC-derived CMs. We observed a significant weakening of force generation after removal of a Z-disc. However, no significant changes of the number of contractions after manipulation were detected. The stress related gene NF-kB was significantly upregulated. Additionally, α-actinin (ACTN2) and filamin-C (FLNc) were upregulated, pointing to remodeling of the Z-disc and the sarcomeric cytoskeleton. Ultimately, cardiac troponin I (TNNI3) and cardiac muscle troponin T (TNNT2) were significantly downregulated. Our results allow a better understanding of transcriptional coupling of Z-disc damage and the relation of damage to force generation and can therefore finally pave the way to novel therapies of sarcomeric disorders. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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