Angiotensin II promotes cardiac differentiation of embryonic stem cells via angiotensin type 1 receptor.
As embryonic stem cells (ESCs) represent an attractive candidate cell source for obtaining cardiomyocytes to be used in cell replacement therapy, it is thus of considerable importance to understand the mechanism by which cardiac differentiation is regulated. In previous studies, we have shown that angiotensin type 1 receptor (AT1R) expressed in cardiomyocytes derived from mouse embryonic stem cells. However, little is known about the role of AT1R in cardiac differentiation, which plays a key role in cardiac physiology and pharmacology. In the present study, we demonstrated that AT1R agonist significantly enhanced cardiac differentiation as determined by increased percentage of beating embryoid bodies and a higher expression level of cardiac markers. On the contrary, AT1R agonist stimulated differentiation was reversed in the presence of AT1R antagonist. In addition, by administering selective inhibitors we found that the effect of AT1R was driven via extracellular-signal regulated kinase, c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase pathways. These findings suggest that AT1R signaling plays a key role in cardiac differentiation of ESCs.
Department of Cardiology, Peking University Third Hospital, Beijing 100191, China.
Liyuan
L
Wu
Zhuqing
Z
Jia
Lihui
L
Yan
Weiping
W
Wang
Jiaji
J
Wang
Yongzhen
Y
Zhang
Chunyan
C
Zhou
D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002454:Cell Differentiation; D058732:Embryoid Bodies / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D051379:Mice; D032386:Myoblasts, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019808:Losartan; D001205:Ascorbic Acid
AT1R; Ang II; Angiotensin type 1 receptor; Cardiac differentiation; ERK; ESCs; Embryonic stem cell; Extracellular-signal regulated kinase; JNK; MAPK; P38 mitogen-activated protein kinase; angiotensin II; angiotensin type 1 receptor; c-Jun NH2-terminal kinase; embryonic stem cells; extracellular-signal regulated kinase; mitogen-activated protein kinase