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The effect of utrophin on the electrophysiological properties of DMD hiPSC-derived cardiomyocytes

ABSTRACT: DMD is a genetic disease, which leads to muscle weakness and cardiomyopathy. The latter remains incurable, being the main cause of death in DMD, therefore new therapeutic strategies are being sought to provide effective treatment. One of them considers upregulation of utrophin, a protein structurally and functionally homologous to dystrophin. In this study proteomic analysis of dystrophin-deficient and both dystrophin- and utrophin-deficient hiPSC-CM indicated on considerable differences in terms of contraction-related mechanisms. We thus investigated the role of utrophin in the maintenance of electrophysiological properties of DMD hiPSC-CM using the cells with additional utrophin deficiency and with utrophin upregulation. Obtained results indicated on disturbance of calcium handling in DMD hiPSC-CM, even more pronounced in DMD/UTRN KO hiPSC-CM and increased values of AHP in DMD hiPSC-CM. Utrophin upregulation improved both calcium oscillations and AHP values. Our findings highlight utrophin as important in the maintenance of the electrophysiological properties of DMD hiPSC-CM.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart

SUBMITTER: Luisa Marie Schmidt

LAB HEAD: Józef Dulak

PROVIDER: PXD044407 | Pride | 2024-06-20

REPOSITORIES: Pride

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			Action	DRS
	DMD01.raw	Raw
	DMD02.raw	Raw
	DMD03.raw	Raw
	Tables.zip	Other
	UTRN01.raw	Raw

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