Optogenetic control of YAP can enhance the rate of wound healing.

Autor: Toh PJY; Mechanobiology Institute, National University of Singapore, Singapore, Singapore.; Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark., Sudol M; Mechanobiology Institute, National University of Singapore, Singapore, Singapore.; Icahn School of Medicine at Mount Sinai, New York, NY, USA., Saunders TE; Mechanobiology Institute, National University of Singapore, Singapore, Singapore. timothy.saunders@warwick.ac.uk.; Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore. timothy.saunders@warwick.ac.uk.; Warwick Medical School, University of Warwick, Coventry, UK. timothy.saunders@warwick.ac.uk.
Jazyk: angličtina
Zdroj: Cellular & molecular biology letters [Cell Mol Biol Lett] 2023 May 11; Vol. 28 (1), pp. 39. Date of Electronic Publication: 2023 May 11.
DOI: 10.1186/s11658-023-00446-9
Abstrakt: Background: Tissues need to regenerate to restore function after injury. Yet, this regenerative capacity varies significantly between organs and between species. For example, in the heart, some species retain full regenerative capacity throughout their lifespan but human cardiac cells display a limited ability to repair the injury. After a myocardial infarction, the function of cardiomyocytes is impaired and reduces the ability of the heart to pump, causing heart failure. Therefore, there is a need to restore the function of an injured heart post myocardial infarction. We investigate in cell culture the role of the Yes-associated protein (YAP), a transcriptional co-regulator with a pivotal role in growth, in driving repair after injury.
Methods: We express optogenetic YAP (optoYAP) in three different cell lines. We characterised the behaviour and function of optoYAP using fluorescence imaging and quantitative real-time PCR of downstream YAP target genes. Mutant constructs were generated using site-directed mutagenesis. Nuclear localised optoYAP was functionally tested using wound healing assay.
Results: Utilising optoYAP, which enables precise control of pathway activation, we show that YAP induces the expression of downstream genes involved in proliferation and migration. optoYAP can increase the speed of wound healing in H9c2 cardiomyoblasts. Interestingly, this is not driven by an increase in proliferation, but by collective cell migration. We subsequently dissect specific phosphorylation sites in YAP to identify the molecular driver of accelerated healing.
Conclusions: This study shows that optogenetic YAP is functional in H9c2 cardiomyoblasts and its controlled activation can potentially enhance wound healing in a range of conditions.
(© 2023. Crown.)
Databáze: MEDLINE
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