Role of TRPV4 in cyclic stretch-induced cell realignment of human embryonic stem cell-derived cardiomyocytes
Refereed conference paper presented and published in conference proceedings




Mechanical stretch produced
by heart regulates cell orientation and alignment and promotes cardiomyocyte
maturity. Stretch-activated calcium channels may play a role in this cell
alignment process. This study was conducted to explore the role of TRP isoforms
in cell alignment of human embryonic stem cell-derived cardiomyocytes
(hESC-CMs). Results: (1) Microarray and RT-PCR showed the expression of TRPV4,
TRPP2 and TRPM2 in hESCs; (2) A selective TRPV4 agonist 4α-PDD elicited a
cytosolic Ca2+ rise in hESC-CM, this Ca2+ rise was blocked by specific TRPV4
antagonists RN1734 and HC067047. Lentiviral-mediated overexpression of TRPV4
prolonged the 4α-PDD-induced [Ca2+]i rise, whereas a dominant negative
construct of TRPV4 (lenti-TRPV4-DN) markedly suppressed the 4α-PDD-induced
[Ca2+]i rise; (3) Uniaxial static stretch induced a rapid and transient [Ca2+]i
rise in hESC-CMs, treatment with RN1734 or HC067047 reduced the stretch-induced
[Ca2+]i rise by about 53% and 70%, respectively. Lenti-TRPV4-DN suppressed the
stretch-induced [Ca2+]i rise by about 42%; (4) Uniaxial cyclic stretch resulted
in cell realignment of hESC-CMs, RN1734 and HC067047 completely abolished the
cyclic stretch-induced cell realignment; (5) Akt phosphorylation was found to
be a downstream signal of TRPV4 . Conclusions: In summary, the present study
demonstrated a predominant role of TRPV4 channel in determining the cyclic
stretch-induced realignment of hESC-CMs, suggesting a crucial role of TRPV4 in
heart development.

著者Li ZC, Yao XQ
會議名稱UPMT Independent Meeting
會議地點Universita Del Salento, Lecce

上次更新時間 2018-21-01 於 21:37