RRC ID 78830
Author Kitakaze T, Tatsumi R, Yamaguchi M, Nakatsuji A, Harada N, Yamaji R.
Title All-Trans Retinoic Acid-Responsive LGR6 Is Transiently Expressed during Myogenic Differentiation and Is Required for Myoblast Differentiation and Fusion.
Journal Int J Mol Sci
Abstract All-trans retinoic acid (ATRA) promotes myoblast differentiation into myotubes. Leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) is a candidate ATRA-responsive gene; however, its role in skeletal muscles remains unclear. Here, we demonstrated that during the differentiation of murine C2C12 myoblasts into myotubes, Lgr6 mRNA expression transiently increased before the increase in the expression of the mRNAs encoding myogenic regulatory factors, such as myogenin, myomaker, and myomerger. The loss of LGR6 decreased the differentiation and fusion indices. The exogenous expression of LGR6 up to 3 and 24 h after the induction of differentiation increased and decreased the mRNA levels of myogenin, myomaker, and myomerger, respectively. Lgr6 mRNA was transiently expressed after myogenic differentiation in the presence of a retinoic acid receptor α (RARα) agonist and an RARγ agonist in addition to ATRA, but not in the absence of ATRA. Furthermore, a proteasome inhibitor or Znfr3 knockdown increased exogenous LGR6 expression. The loss of LGR6 attenuated the Wnt/β-catenin signaling activity induced by Wnt3a alone or in combination with Wnt3a and R-spondin 2. These results indicate that LGR6 promotes myogenic differentiation and that ATRA is required for the transient expression of LGR6 during differentiation. Furthermore, LGR6 expression appeared to be downregulated by the ubiquitin-proteasome system involving ZNRF3.
Volume 24(10)
Published 2023-5-20
DOI 10.3390/ijms24109035
PII ijms24109035
PMID 37240382
PMC PMC10219391
MeSH Animals Cell Differentiation / genetics Mice Myoblasts / metabolism Myogenin / genetics Myogenin / metabolism RNA, Messenger / genetics Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / metabolism Tretinoin* / metabolism Tretinoin* / pharmacology Wnt Signaling Pathway*
Human and Animal Cells C2C12(RCB0987)