Acute effect of endothelins on intercellular communication of human embryonic stem cells.
Endothelin (ET) family comprises three isoforms, ET-1, ET-2 and ET-3 that bind to two receptors ET-A and ET-B. Upon hESC differentiation, ET-1 and ET-B are respectively up- and down-regulated, suggesting a potential role of ETs in hESC biology. Here we show expression of ET receptors in hESC and demonstrate that ET-1 and ET-2 inhibit gap junctional intercellular communication (GJIC), while ET-3 does not. Pre-incubation of the cell cultures with the two specific antagonists of ET-A and ET-B, BQ123 and BQ788 respectively, demonstrate that inhibition of GJIC by ETs is mediated by ET-A. Long-term treatment of hESC with ET-1 indicates no visible effect on hESC maintenance of pluripotency markers, as assessed by expression of the hESC markers Oct-4, GCTM-2 and TG-30. Altogether these data show that hESC are target cells of ETs.
Wong
Raymond C B
RC
Centre for Neuroscience, Department of Pharmacology, The University of Melbourne, Parkville, VIC 3010, Australia.
Davidson
Kathryn C
KC
Leung
Jessie
J
Pera
Martin F
MF
Pébay
Alice
A
D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology; D016232:Endothelins; D017629:Gap Junctions; D000066449:Human Embryonic Stem Cells; D006801:Humans
D016232:Endothelins