Dose-Dependent Antiteratogenic Effects of Folic Acid on All-Trans Retinoic Acid-Induced Cleft Palate in Fetal Mice

2016 ◽  
Vol 53 (6) ◽  
pp. 720-726 ◽  
Author(s):  
Huijing Wang ◽  
Weiliang Chen
Keyword(s):  
Folic Acid ◽  
Retinoic Acid ◽  
Cleft Palate ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Fetal Mice ◽  
Dose Dependent

EFFECT OF FETAL EXPOSURE OF ALL-TRANS RETINOIC ACID ON DNA METHYLATION IN MOUSE FETUSES WITH CLEFT PALATE

2007 ◽  
Vol 77 (Suppl_1) ◽  
pp. 162-162
Author(s):  
Yoshiharu Matsuno ◽  
Motone Kuriyama ◽  
Hideki Fukata ◽  
Koji Sato ◽  
Chisato Mori
Keyword(s):  
Dna Methylation ◽  
Retinoic Acid ◽  
Cleft Palate ◽  
Fetal Exposure ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Mouse Fetuses

Folic acid rescues all‐trans retinoic acid‐induced anorectal malformations in rats

2020 ◽  
Vol 112 (20) ◽  
pp. 1850-1856
Author(s):  
Fang Wu ◽  
Chenchao Gu ◽  
Yang Bi ◽  
Zhenhua Guo ◽  
Yi Wang
Keyword(s):  
Folic Acid ◽  
Retinoic Acid ◽  
Anorectal Malformations ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Developmental anomalies induced by all-trans retinoic acid in fetal mice: I. Macroscopic findings

Teratology ◽  
1986 ◽  
Vol 34 (1) ◽  
pp. 37-49 ◽  
Author(s):  
Yoshiko Yasuda ◽  
Masaharu Okamoto ◽  
Hiroyoshi Konishi ◽  
Takuya Matsuo ◽  
Takahide Kihara ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Developmental Anomalies ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Fetal Mice ◽  
Macroscopic Findings

LncRNA H19-mediated mouse cleft palate induced by all-trans retinoic acid

2016 ◽  
Vol 36 (4) ◽  
pp. 395-401 ◽  
Author(s):  
L Gao ◽  
Y Liu ◽  
Y Wen ◽  
W Wu
Keyword(s):  
Retinoic Acid ◽  
Cleft Palate ◽  
Target Gene ◽  
Functional Roles ◽  
New Class ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Age Related ◽  
And Control

Long noncoding RNAs (lncRNAs) are the new class of transcripts and pervasively transcribed in the genome, which have been found to play important functional roles in many tissues and organs. LncRNAs can interact with target gene to exert their functions. However, the function and mechanism of lncRNA in cleft palate (CP) development remain elusive. Here, we investigated the role of lncRNA H19 and its target gene insulin-like growth factor 2 (IGF2) in CP of mice. All-trans retinoic acid (atRA) is a well-known teratogenic effecter of CP. After establishment of the CP mouse model using atRA in vivo, we found that the rate of CP in mice was 100%. The tail lengths of fetuses in atRA-treated mice were shorter than those of control mice from embryonic day (E)12 to E17. The expression of lncRNA H19 and IGF2 were embryo age-related differences between atRNA-treated and control mice. In addition, the the relationship between lncRNA H19 and IGF2 were negative correlation in the critical period of developmental palate. These findings suggest that lncRNA H19 mediate atRA-induced CP in mice.

scholarly journals All-trans Retinoic Acid Regulates miR-106a-5p Inhibition of Autophagic in Developing Cleft Palates

2020 ◽  
Author(s):  
Lungang Shi ◽  
Yan Liang ◽  
Lijing Yang ◽  
Binchen Li ◽  
Binna Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Cleft Palate ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Differentiation Potential ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Pten Mrna

AbstractBackgroundAll-trans retinoic acid (atRA) results in cleft palate, but the cellular and molecular mechanisms underlying the teratogenic effects on palatal development have not been fully elucidated. Autophagy interruption has been reported to seriously affect embryonic-cell differentiation and development. This study aimed to verify whether atRA-induced cleft palate occurs because atRA blocks autophagy and stemness of embryonic palatal mesenchyme (MEPM) cells, which are maintained via the phosphatase and tensin homolog (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) autophagic signaling pathway, and inhibits osteogenic-differentiation potential of MEPM cells, which could lead to the development of cleft palate.MethodsTo assess the stemness and pluripotency of MEPM cells, we analyzed their surfacemarkers using immunofluorescence (IF) and flow cytometry (FCM). Differentiation potentials, such as osteogenic, adipogenic, and chondrogenic differentiation, were induced. We also investigated the role of the PTEN/Akt/mTOR autophagic signaling pathway, which maintains the stemness and pluripotency of MEPM cells. Using transmission electron microscopy (TEM), Western blot analysis, quantitative reverse transcriptase polymerase chain reaction (RT-qPCR), messenger ribonucleic acid (mRNA) microarray, dual-luciferase reporter system, and exosomes, we found that atRA blocks autophagy and osteogenic differentiation of MEPM cells through micro-ribonucleic acid (miR)-106a-5p by targeting the PTEN/Akt/mTOR autophagic pathway.ResultsIn vitro purified MEPM cells expressed cell surface markers similar to those of mouse bone marrow stem cells. Additionally, in vitro MEPM cells were ectomesenchymal and expressed the neural-crest marker human natural killer-1 (HNK-1), the mesodermal marker vimentin, and the ectodermal marker nestin. They were also positive for in vitro MEPM markers, including platelet-derived growth factor alpha (PDGFRα), ephrin B1 (Efnb1), odd-skipped related 2 (Osr2), and Meox2, as well as for stemness markers including POU class 5 homeobox 4 (Oct4), Nanog, and sex-determining region Y-related HMG box 2 (Sox2). MEPM cell pluripotency was retained through activation of the PTEN/Akt/mTOR autophagic signaling pathway. We found that atRA blocked MEPM cell pluripotency to inhibit osteogenic differentiation via miR-106a-5p targeting of PTEN mRNA and subsequent suppression of the PTEN/Akt/mTOR autophagic pathway.ConclusionsIn vitro cultured MEPM cells are ectomesenchymal stem cells that have strong osteogenic differentiation potential, and MEPM pluripotency is regulated by autophagy via the PTEN/AKT/mTOR signaling pathway. atRA disrupts MEPM cell pluripotency through PTEN/AKT/mTOR signaling inactivation where miR-106a-5p targets PTEN mRNA to reduce osteogenic differentiation of MEPM cells and results in the development of cleft palates. Our findings provide new insight into the mechanism underlying the development of cleft palate, and miR-106a-5p may act as a prenatal screening biomarker for cleft palate as well as a new diagnostic and therapeutic target.

scholarly journals Excessive All-Trans Retinoic Acid Inhibits Cell Proliferation Through Upregulated MicroRNA-4680-3p in Cultured Human Palate Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Hiroki Yoshioka ◽  
Sai Shankar Ramakrishnan ◽  
Junbo Shim ◽  
Akiko Suzuki ◽  
Junichi Iwata
Keyword(s):  
Cell Proliferation ◽  
Retinoic Acid ◽  
Cleft Palate ◽  
Specific Inhibitor ◽  
Dependent Manner ◽  
Altered Expression ◽  
Expression Of Genes ◽  
All Trans Retinoic Acid ◽  
Congenital Birth Defect ◽  
Dose Dependent

Cleft palate is the second most common congenital birth defect, and both environmental and genetic factors are involved in the etiology of the disease. However, it remains largely unknown how environmental factors affect palate development. Our previous studies show that several microRNAs (miRs) suppress the expression of genes involved in cleft palate. Here we show that miR-4680-3p plays a crucial role in cleft palate pathogenesis. We found that all-trans retinoic acid (atRA) specifically induces miR-4680-3p in cultured human embryonic palatal mesenchymal (HEPM) cells. Overexpression of miR-4680-3p inhibited cell proliferation in a dose-dependent manner through the suppression of expression of ERBB2 and JADE1, which are known cleft palate-related genes. Importantly, a miR-4680-3p-specific inhibitor normalized cell proliferation and altered expression of ERBB2 and JADE1 in cells treated with atRA. Taken together, our results suggest that upregulation of miR-4680-3p induced by atRA may cause cleft palate through suppression of ERBB2 and JADE1. Thus, miRs may be potential targets for the prevention and diagnosis of cleft palate.

scholarly journals Involvement of RBP4 in all-trans retinoic acid induced cleft palate

2017 ◽  
Vol 16 (5) ◽  
pp. 5915-5923 ◽  
Author(s):  
Shiyi Dong ◽  
Yadong Zhang ◽  
Hongzhang Huang
Keyword(s):  
Retinoic Acid ◽  
Cleft Palate ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid
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