Uniaxial cyclic stretch stimulates TRPV4 to induce realignment of human embryonic stem cell-derived cardiomyocytes
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AbstractHuman pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) in culture are randomly organized and do not typically show directional alignment. In the present study, we used uniaxial cyclic stretch to facilitate the alignment of cultured human embryonic stem cell-derived cardiomyocytes (hESC-CMs), so that these cells can be more adult-like for potential future application in drug screening and in vitro studies of cardiac function. We then explored the functional role of mechanosensitive TRPV4 channels in cyclic stretch-induced realignment of hESC-CMs. RT-PCR, immunoblots and immunostaining detected TRPV4 expression in these cells. 4α-phorbol 12,13-didecanoate (4α-PDD), a TRPV4 agonist, elicited a cytosolic Ca2+ ([Ca2+]i) rise, the effect of which was abolished by TRPV4 inhibitors RN1734 and HC067047, and a TRPV4 dominant negative construct. These results confirmed the functional presence of TRPV4 in these cells. Importantly, longitudinal stretch was found to induce a [Ca2+]i rise, the effect of which was inhibited by TRPV4 antagonists. Furthermore, uniaxial cyclic stretch for 2h induced realignment of hESC-CMs in the direction transverse to the direction of stretch, the effect of which was also abolished by TRPV4 antagonists. Akt phosphorylation was found to be a downstream signal of TRPV4. Taken together, these data strongly suggest endogenous TRPV4 channels as a mechanosensor, mediating cyclic stretch-induced realignment of hESC-CMs.
All Author(s) ListQi Y., Li Z., Kong C.-W., Tang N.L., Huang Y., Li R.A., Yao X.
Journal nameJournal of Molecular and Cellular Cardiology
Volume Number87
PublisherAcademic Press
Place of PublicationUnited States
Pages65 - 73
LanguagesEnglish-United Kingdom
KeywordsCardiomyocyte alignment, Human embryonic stem cells, PI3K-Akt signaling pathway, TRPV4 channel

Last updated on 2020-21-11 at 01:30