TY - JOUR
T1 - Cyclic mechanical strain maintains Nanog expression through PI3K/Akt signaling in mouse embryonic stem cells
AU - Horiuchi, Rie
AU - Akimoto, Takayuki
AU - Hong, Zhang
AU - Ushida, Takashi
PY - 2012/8/15
Y1 - 2012/8/15
N2 - Mechanical strain has been reported to affect the proliferation/differentiation of many cell types; however, the effects of mechanotransduction on self-renewal as well as pluripotency of embryonic stem (ES) cells remains unknown. To investigate the effects of mechanical strain on mouse ES cell fate, we examined the expression of Nanog, which is an essential regulator of self-renewal and pluripotency as well as Nanog-associated intracellular signaling during uniaxial cyclic mechanical strain. The mouse ES cell line, CCE was plated onto elastic membranes, and we applied 10% strain at 0.17. Hz. The expression of Nanog was reduced during ES cell differentiation in response to the withdrawal of leukemia inhibitory factor (LIF); however, two days of cyclic mechanical strain attenuated this reduction of Nanog expression. On the other hand, the cyclic mechanical strain promoted PI3K-Akt signaling, which is reported as an upstream of Nanog transcription. The cyclic mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor wortmannin. Furthermore, cytochalasin D, an inhibitor of actin polymerization, also inhibited the mechanical strain-induced increase in phospho-Akt. These findings imply that mechanical force plays a role in regulating Nanog expression in ES cells through the actin cytoskeleton-PI3K-Akt signaling.
AB - Mechanical strain has been reported to affect the proliferation/differentiation of many cell types; however, the effects of mechanotransduction on self-renewal as well as pluripotency of embryonic stem (ES) cells remains unknown. To investigate the effects of mechanical strain on mouse ES cell fate, we examined the expression of Nanog, which is an essential regulator of self-renewal and pluripotency as well as Nanog-associated intracellular signaling during uniaxial cyclic mechanical strain. The mouse ES cell line, CCE was plated onto elastic membranes, and we applied 10% strain at 0.17. Hz. The expression of Nanog was reduced during ES cell differentiation in response to the withdrawal of leukemia inhibitory factor (LIF); however, two days of cyclic mechanical strain attenuated this reduction of Nanog expression. On the other hand, the cyclic mechanical strain promoted PI3K-Akt signaling, which is reported as an upstream of Nanog transcription. The cyclic mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor wortmannin. Furthermore, cytochalasin D, an inhibitor of actin polymerization, also inhibited the mechanical strain-induced increase in phospho-Akt. These findings imply that mechanical force plays a role in regulating Nanog expression in ES cells through the actin cytoskeleton-PI3K-Akt signaling.
KW - Actin
KW - Embryonic germ (EG)
KW - Embryonic stem (ES)
KW - Focal adhesion kinase (FAK)
KW - Mechano-transduction
KW - Mechanobiology
KW - Stemness
KW - Stretch
UR - http://www.scopus.com/inward/record.url?scp=84862892940&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862892940&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2012.05.021
DO - 10.1016/j.yexcr.2012.05.021
M3 - Article
C2 - 22683858
AN - SCOPUS:84862892940
VL - 318
SP - 1726
EP - 1732
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 14
ER -