TY - JOUR
T1 - IRE1-XBP1 pathway of the unfolded protein response is required during early differentiation of C2C12 myoblasts
AU - Tokutake, Yukako
AU - Yamada, Keita
AU - Hayashi, Satoko
AU - Arai, Wataru
AU - Watanabe, Takafumi
AU - Yonekura, Shinichi
N1 - Funding Information:
Funding: This research was funded in part by Grant-in-Aid for JSPS Fellows, grant number 16J11238 and Grant-in-Aid for Scientific Research (C), grant number 17K08042.
Funding Information:
This research was funded in part by Grant-in-Aid for JSPS Fellows, grant number 16J11238 and Grant-in-Aid for Scientific Research (C), grant number 17K08042.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - In skeletal muscle, myoblast differentiation results in the formation of multinucleated myofibers. Although recent studies have shown that unfolded protein responses (UPRs) play an important role in intracellular remodeling and contribute to skeletal muscle differentiation, the involvement of IRE1–XBP1 signaling, a major UPR signaling pathway, remains unclear. This study aimed to investigate the effect of the IRE1–XBP1 pathway on skeletal muscle differentiation. In C2C12 cells, knockdown of IRE1 and XBP1 in cells remarkably suppressed differentiation. In addition, apoptosis and autophagy were dramatically enhanced in the XBP1-knockdown cells, highlighting the participation of IRE1–XBP1 in cell survival maintenance with differentiation stimuli during skeletal muscle differentiation. In myogenic cells, we demonstrated that the expression of CDK5 (cyclin-dependent kinase 5) is regulated by XBP1s, and we propose that XBP1 regulates the expression of MyoD family genes via the induction of CDK5. In conclusion, this study revealed that IRE1–XBP1 signaling plays critical roles in cell viability and the expression of differentiation-related genes in predifferentiated myoblasts and during the early differentiation phase.
AB - In skeletal muscle, myoblast differentiation results in the formation of multinucleated myofibers. Although recent studies have shown that unfolded protein responses (UPRs) play an important role in intracellular remodeling and contribute to skeletal muscle differentiation, the involvement of IRE1–XBP1 signaling, a major UPR signaling pathway, remains unclear. This study aimed to investigate the effect of the IRE1–XBP1 pathway on skeletal muscle differentiation. In C2C12 cells, knockdown of IRE1 and XBP1 in cells remarkably suppressed differentiation. In addition, apoptosis and autophagy were dramatically enhanced in the XBP1-knockdown cells, highlighting the participation of IRE1–XBP1 in cell survival maintenance with differentiation stimuli during skeletal muscle differentiation. In myogenic cells, we demonstrated that the expression of CDK5 (cyclin-dependent kinase 5) is regulated by XBP1s, and we propose that XBP1 regulates the expression of MyoD family genes via the induction of CDK5. In conclusion, this study revealed that IRE1–XBP1 signaling plays critical roles in cell viability and the expression of differentiation-related genes in predifferentiated myoblasts and during the early differentiation phase.
KW - Apoptosis
KW - Autophagy
KW - Skeletal muscle differentiation
KW - Unfolded protein response (UPR)
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U2 - 10.3390/ijms21010182
DO - 10.3390/ijms21010182
M3 - Article
C2 - 31888027
AN - SCOPUS:85077334835
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 1
M1 - 182
ER -