1. Interaction between retinoic acid and FGF/ERK signals are involved in Dexamethasone-induced abnormal myogenesis during embryonic development.
- Author
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Xu S, He X, Shi J, Li Z, Song J, Wang J, Wang G, Brand-Saberi B, Cheng X, and Yang X
- Subjects
- Animals, Cell Differentiation drug effects, Cell Line, Cell Proliferation drug effects, Chick Embryo, Female, Fibroblast Growth Factors metabolism, MAP Kinase Signaling System drug effects, Mice, Myoblasts cytology, Myoblasts drug effects, Pregnancy, Signal Transduction drug effects, Tretinoin metabolism, Up-Regulation drug effects, Dexamethasone toxicity, Embryonic Development drug effects, Glucocorticoids toxicity, Muscle Development drug effects
- Abstract
Despite the common application in pregnancy at clinical practice, it remains ambiguous whether dexamethasone (Dex) exposure can affect embryonic myogenesis. In this study, firstly we showed that 10
-6 M Dex (Cheng et al., 2016; 2017) treatment resulted in abnormal myogenesis in chicken embryos. Secondly, we demonstrated that 10-6 M Dex-induced abnormality of myogenesis resulted from aberrant cell proliferation, as well as from alteration of the differentiation process from the early stage of somitogenesis up to the late stage of myogenesis. The above-mentioned results caused by Dex exposure might be due to the aberrant gene expressions of somite formation (Raldh2, Fgf8, Wnt3a, β-catenin, Slug, Paraxis, N-cadherin) and differentiation (Pax3, MyoD, Wnt3a, Msx1, Shh). Thirdly, RNA sequencing implied the statistically significant differential gene expressions in regulating the myofibril and systemic development, as well as a dramatical alteration of retinoic acid (RA) signaling during somite development in the chicken embryos exposed to Dex. The subsequent validation experiments verified that Dex treatment indeed led to a metabolic change of RA signaling, which was up-regulated and principally mediated by FGF-ERK signaling revealed by means of the combination of chicken embryos and in vitro C2C12 cells. These findings highlight that 10-6 M Dex exposure enhances the risk of abnormal myogenesis through interfering with RA signaling during development., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
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