Functional specificity of the two retinoic acid receptor RAR and RXR families in myogenesis

Alric, Séverine; Froeschle, Anne; Piquemal, David; Carnac, Gilles; Bonnieu, Anne

doi:10.1038/sj.onc.1201484

Cited by 28 publications

(17 citation statements)

References 49 publications

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“…3, 4). Previous study indicated that 1µM RA can promote ex vivo myogenic differentiation of myoblast by inducing MyoD and Myogenin transcription 16) , which was confirmed again by our studies. In future, we would further quantify MyoD and Myogenin in respect of myogenic differentiation on protein level.…”

Section: Discussionsupporting

confidence: 91%

Effects of Excessive Retinoic Acid on C2C12 Myogenesis

Liu

Jiang

et al. 2016

J. Hard Tissue Biology.

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Retinoic acid (RA) is a widely-used agent inducing cell differentiation. In order to study the effect of excessive RA on myogenesis, C2C12 cells were cultured in gradient concentrations of RA. In this study, the cell cycle arrested in G 0 /G 1 phase when the concentration of RA was higher than 10 µM. Cell proliferation was inhibited by RA over 40 µM. Therefore, 1 and 10 µM RA were chosen to treat C2C12 cells under serum withdrawal, respectively, and then, myogenic regulatory factors (MRFs) were measured by real-time PCR. It was found that after RA treatment, Myf5 transcription was maintained in a lower level. The change curves of MyoD and Myogenin transcription were consistent with the vehicle control, but MRF4 transcription was higher than that of the vehicle control at day 6. Additionally, compared with 10 µM RA-treated cells, the elevated transcription of MyoD and Myogenin insisted longer and the transcription of MRF4 at 6 day was higher in 1 µM RA-treated cells. Myosin heavy chain (MyHC) was also calibrated by Western blot to analysis myogenic terminal differentiation. Our findings illustrated that MyHC protein level was obviously declined in 10 µM RA-treated cells. Finally, immunostaining revealed that a growing number of bifurcations in RA-treated myosin-positive cells were accompanied by longer and thinner cell bodies, especially in 10µM RA-treated cells. In conclusion, excessive RA could still induce myoblast myogenic differentiation. However, the maturation of myotubes might be discouraged by a higher-dose of RA.

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Section: Discussionsupporting

confidence: 91%

Effects of Excessive Retinoic Acid on C2C12 Myogenesis

Liu

Jiang

et al. 2016

J. Hard Tissue Biology.

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“…Interestingly, pluripotent embryonal carcinoma (EC) cells containing a dominant negative RARα that blocks the DNA binding capacity of the receptor [36, 37], are not able to commit to the skeletal muscle lineage but can undergo neuronal differentiation following RA induction [38, 39]. However, RXR, but not RAR, is essential for the differentiation of skeletal myoblasts [40]. Moreover, knockdown of RXRα attenuates rexinoid-promoted myoblast differentiation and fusion [41].…”

Section: Roles Of Nuclear Receptors In Cellular Functionmentioning

confidence: 99%

Gene expression profiling discerns molecular pathways elicited by ligand signaling to enhance the specification of embryonic stem cells into skeletal muscle lineage

Dixon

Chen

2017

Cell Biosci

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Regulation of lineage specification and differentiation in embryonic stem (ES) cells can be achieved through the activation of endogenous signaling, an avenue for potential application in regenerative medicine. During vertebrate development, retinoic acid (RA) plays an important role in body axis elongation and mesoderm segmentation in that graded exposure to RA provides cells with positional identity and directs commitment to specific tissue lineages. Nevertheless, bexarotene, a clinically approved rexinoid, enhances the specification and differentiation of ES cells into skeletal myocytes more effectively than RA. Thus profiling the transcriptomes of ES cells differentiated with bexarotene or RA permits the identification of different genetic targets and signaling pathways that may contribute to the difference of bexarotene and RA in efficiency of myogenesis. Interestingly, bexarotene induces the early expression of a myogenic progenitor marker, Meox1, while the expression of many RA targets is also enhanced by bexarotene. Several signaling molecules involved in the progression of myogenic specification and commitment are differentially regulated by bexarotene and RA, suggesting that early targets of rexinoid allow the coordinated regulation of molecular events which leads to efficient myogenic differentiation in ES cells.

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“…Nuclear hormone receptors have also been shown to assist myogenesis (Muscat et al, 1995). The importance of thyroid hormone (TH) and retinoic acid receptors (RAR and RXR) in myogenic differentiation has been established by several studies, showing that TH and RAR/RXR responsive elements are functionally relevant for the activation of muscle-specific promoters Albagli-Curiel et al, 1993;Downes et al, 1993;Halevy and Lerman, 1993;Downes et al, 1994;Alric et al, 1998). However, other studies indicate that the effect of retinoic acid (RA) on myogenesis in vivo may be more complex and might depend on the influence of other extracellular signals (Xiao et al, 1995).…”

Section: Positive Regulators Of Myogenesismentioning

confidence: 99%

Regulation of muscle regulatory factors by DNA-binding, interacting proteins, and post-transcriptional modifications

2000

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Skeletal muscle differentiation is influenced by multiple pathways, which regulate the activity of myogenic regulatory factors (MRFs)-the myogenic basic helix-loop-helix proteins and the MEF2-family members-in positive or negative ways. Here we will review and discuss the network of signals that regulate MRF function during myocyte proliferation, differentiation, and post-mitotic growth. Elucidating the mechanisms governing muscle-specific transcription will provide important insight in better understanding the embryonic development of muscle at the molecular level and will have important implications in setting out strategies aimed at muscle regeneration. Since the activity of MRFs are compromised in tumors of myogenic derivation-the rhabdomyosarcomas-the studies summarized in this review can provide a useful tool to uncover the molecular basis underlying the formation of these tumors.

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Functional specificity of the two retinoic acid receptor RAR and RXR families in myogenesis

Cited by 28 publications

References 49 publications

Effects of Excessive Retinoic Acid on C2C12 Myogenesis

Effects of Excessive Retinoic Acid on C2C12 Myogenesis

Gene expression profiling discerns molecular pathways elicited by ligand signaling to enhance the specification of embryonic stem cells into skeletal muscle lineage

Regulation of muscle regulatory factors by DNA-binding, interacting proteins, and post-transcriptional modifications

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