scholarly journals Dysbacteriosis-Derived Lipopolysaccharide Causes Embryonic Osteopenia through Retinoic-Acid-Regulated DLX5 Expression

2020 ◽  
Vol 21 (7) ◽  
pp. 2518
Author(s):  
Lingsen You ◽  
Liwei Zhu ◽  
Pei-zhi Li ◽  
Guang Wang ◽  
Hongmei Cai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Gut Microbiota ◽  
Retinoic Acid Receptor ◽  
Immunofluorescent Staining ◽  
Inflammatory Factors ◽  
Mineral Density ◽  
Alizarin Red ◽  
Gut Microbiota Dysbiosis ◽  
Lps Treatment

Growing evidence suggests an adverse impact of gut microbiota dysbiosis on human health. However, it remains unclear whether embryonic osteogenesis is affected by maternal gut dysbacteriosis. In this study, we observed that elevated lipopolysaccharide (LPS) levels led to skeletal developmental retardation in an established mouse model of gut microbiota dysbiosis. Using chick embryos exposed to dysbacteriosis-derived LPS, we found restriction in the development of long bones as demonstrated by Alcian blue and alizarin red staining. Micro-CT and histological analysis exhibited decreased trabecular volume, bone mineral density, and collagen production, as well as suppressed osteoblastic gene expression (Ocn, Runx2, Osx, and Dlx5) in chick embryonic phalanges following LPS treatment. Atomic force microscopy manifested decreased roughness of MC3T3-E1 cells and poorly developed matrix vesicles (MVs) in presence of LPS. The expression of the aforementioned osteoblastic genes was suppressed in MC3T3-E1 cells as well. High-throughput RNA sequencing indicated that retinoic acid (RA) may play an important role in LPS-induced osteopenia. The addition of RA suppressed Dlx5 expression in MC3T3-E1 cells, as was also seen when exposed to LPS. Quantitative PCR, Western blot, and immunofluorescent staining showed that retinoic acid receptor α (RARα) was upregulated by LPS or RA treatment, while the expression of DLX5 was downregulated. CYP1B1 expression was increased by LPS treatment in MC3T3-E1 cells, which might be attributed to the increased inflammatory factors and subsequently activated NF-κB signaling. Eventually, blocking RA signals with AGN193109 successfully restored LPS-inhibited osteoblastic gene expression. Taken together, our data reveals that maternal gut microbiota dysbiosis can interfere with bone ossification, in which Dlx5 expression regulated by RA signaling plays an important role.

Altered retinoid metabolism gene expression in chronic Stevens-Johnson syndrome

2019 ◽  
Vol 103 (8) ◽  
pp. 1015-1023 ◽  
Author(s):  
Gurumurthy Srividya ◽  
Narayanasamy Angayarkanni ◽  
Geetha Iyer ◽  
Bhaskar Srinivasan ◽  
Shweta Agarwal
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Mucous Membrane ◽  
Retinoic Acid Receptor ◽  
Stevens Johnson Syndrome ◽  
Bulbar Conjunctiva ◽  
Ppar Γ ◽  
Retinoid Metabolism ◽  
Johnson Syndrome ◽  
Alpha 1 Antitrypsin

BackgroundStevens-Johnson syndrome (SJS), a blistering disorder of the skin and mucous membrane, leads to ocular morbidity in >60% of cases. Retinoids are vital micronutrients for vision, regulating corneal and conjunctival cell proliferation, differentiation and immune function. This prospective case–control study probed for alterations in retinoid metabolism by evaluating retinoic acid receptor signalling in the conjunctival cells of patients with SJS.MethodsImprints were collected from the bulbar conjunctiva of patients with chronic SJS. The gene expression of retinoic acid receptors, namely, RXRA, RARA, RARG, RORA; the fibrosis marker TGFβ and its receptor TGFβRII; the transcription factors PPAR-γ, STRA6 and Stat3; the enzymes aldehyde dehydrogenase (ALDH1a1), alpha-1 antitrypsin (A1AT); and the Cyp genes Cyp26a1 and Cyp26b1 were assessed by quantitative PCR in patients with SJS pre-mucous (n = 34) and post-mucous membrane graft (MMG) intervention (n=19) in comparison with age-matched/sex-matched healthy controls (n=20). Western blot analysis of ALDH1a1, RARA and RARG were done in the conjunctival imprint cells.ResultsThe transcript levels of ALDH1a1, RXRA, RORA, STRA6, Cyp26a1 and Cyp26b1 were decreased around 4, 26, 17, 129, 9 and 8 folds, respectively, and RARA, RARG, PPAR-γ, TGFβ, TGFβRII were increased by 12, 15, 51, 16 and 87 folds, respectively, in SJS conjunctiva at the pre-MMG stage. The changes in RORA, Cyp26a1, Cyp26b1, RARA and Stat3 were statistically significant (p<0.05). Changes in protein expression of ALDH1a1, RARA and RARG supported the gene expression changes.ConclusionsThe study provides the first experimental insight into the role of retinoid metabolism in the ocular sequelae of chronic SJS.

scholarly journals The Environmental Light Influences the Circulatory Levels of Retinoic Acid and Associates with Hepatic Lipid Metabolism

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6336-6342 ◽  
Author(s):  
Wenqiang Pang ◽  
Chunying Li ◽  
Yue Zhao ◽  
Shiming Wang ◽  
Wei Dong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Adenosine Receptors ◽  
Light Exposure ◽  
Retinoic Acid Receptor ◽  
Hepatic Lipase ◽  
Mouse Retina ◽  
Acid Receptor ◽  
Hepatic Lipid ◽  
Environmental Light

Environmental light is involved in the regulation of photochemical reaction in mouse retina. It remains unclear whether light-mediated increase in all-trans retinoic acid (ATRA) synthesis in retina will result in altering the circulatory levels of ATRA and regulating downstream gene expression and physiological function. Here we showed circulatory levels of ATRA decreased in mice under constant darkness and elevated by light exposure. Fat gene pancreatic lipase-related protein 2 (mPlrp2) and its partner procolipase (mClps), but not hepatic lipase (mHl), activated in livers for responding to lack of light illuminating. Light-triggered alterations in circulatory ATRA levels regulated ecto-5′-nucleotidase gene expression by retinoic acid receptor retinoic acid receptor-α and modulated 5′-AMP levels in blood and were associated with mPlrp2 and mClps expression in the livers. Mice deficient in adenosine receptors displayed mPlrp2 and mClps expression in livers under 12-h light, 12-h dark cycles. Caffeine blocked adenosine receptors and induced hepatic mPlrp2 and mClps expression in wild-type mice. Mice activated in hepatic mPlrp2 and mClps expression lowered hepatic and serum lipid levels and markedly elevated circulatory levels of all-trans retinol. Our results suggest environmental light influence hepatic lipid homeostasis by light-modulated retinoic acid signaling associated with mPlrp2 and mClps gene expression in livers.

scholarly journals Interplay of Protein Disorder in Retinoic Acid Receptor Heterodimer and Its Corepressor Regulates Gene Expression

Structure ◽  
2019 ◽  
Vol 27 (8) ◽  
pp. 1270-1285.e6 ◽  
Author(s):  
Tiago N. Cordeiro ◽  
Nathalie Sibille ◽  
Pierre Germain ◽  
Philippe Barthe ◽  
Abdelhay Boulahtouf ◽  
...  
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Protein Disorder ◽  
Acid Receptor

scholarly journals Retinoic acid receptor-related orphan receptor (ROR) α4 is the predominant isoform of the nuclear receptor RORα in the liver and is up-regulated by hypoxia in HepG2 human hepatoma cells

2002 ◽  
Vol 364 (2) ◽  
pp. 449-456 ◽  
Author(s):  
Caroline CHAUVET ◽  
Brigitte BOIS-JOYEUX ◽  
Jean-Louis DANAN
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Hepg2 Cells ◽  
Transcriptional Activity ◽  
Cobalt Chloride ◽  
Retinoic Acid Receptor ◽  
Orphan Receptor ◽  
Human Hepatoma ◽  
Human Hepatoma Cells ◽  
Acid Receptor

The retinoic acid receptor-related orphan receptor α (RORα) is critically involved in many physiological functions in several organs. We find that the main RORα isoform in the mouse liver is the RORα4 isoform, in terms of both mRNA and protein levels, while the RORα1 isoform is less abundant. Because hypoxia is a major feature of liver physiology and pathology, we examined the effect of this stress on Rora gene expression and RORα transcriptional activity. HepG2 human hepatoma cells were cultured for 24h under normoxia (20% O2) or hypoxia (10, 2, and 0.1% O2) and the abundance of the Rora transcripts measured by Northern blot and semi-quantitative RT-PCR. Hypoxic HepG2 cells contained more Rora mRNA than controls. This was also observed in rat hepatocytes in primary culture. Cobalt chloride and desferrioxamine also increased the amount of Rora mRNA in HepG2 cells. It is likely that these treatments increase the amount of the RORα4 protein in HepG2 cells as evidenced by Western blotting in the case of desferrioxamine. Transient transfection experiments indicated that hypoxia, cobalt chloride, and desferrioxamine all stimulate RORα transcriptional activity in HepG2 cells. Hence, we believe that RORα participates in the control of gene transcription in hepatic cells and modulates gene expression in response to hypoxic stress.

scholarly journals Synergistic and additive effect of retinoic acid in circumventing resistance to p53 restoration

2018 ◽  
Vol 115 (9) ◽  
pp. 2198-2203 ◽  
Author(s):  
Connie A. Larsson ◽  
Sydney M. Moyer ◽  
Bin Liu ◽  
Keith A. Michel ◽  
Vinod Pant ◽  
...  
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Therapeutic Response ◽  
Retinoic Acid Receptor ◽  
Mutant P53 ◽  
Missense Mutations ◽  
Synthetic Retinoid ◽  
P53 Reactivation

TP53 mutations occur in ∼50% of all human tumors, with increased frequency in aggressive cancers that are notoriously difficult to treat. Additionally, p53 missense mutations are remarkably predictive of refractoriness to chemo/radiotherapy in various malignancies. These observations have led to the development of mutant p53-targeting agents that restore p53 function. An important unknown is which p53-mutant tumors will respond to p53 reactivation-based therapies. Here, we found a heterogeneous impact on therapeutic response to p53 restoration, suggesting that it will unlikely be effective as a monotherapy. Through gene expression profiling of p53R172H-mutant lymphomas, we identified retinoic acid receptor gamma (RARγ) as an actionable target and demonstrated that pharmacological activation of RARγ with a synthetic retinoid sensitizes resistant p53-mutant lymphomas to p53 restoration, while additively improving outcome and survival in inherently sensitive tumors.

scholarly journals Effect of retinoid status on α, β and γ retinoic acid receptor mRNA levels in various rat tissues

1992 ◽  
Vol 286 (3) ◽  
pp. 755-760 ◽  
Author(s):  
S Kato ◽  
H Mano ◽  
T Kumazawa ◽  
Y Yoshizawa ◽  
R Kojima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Vitamin A ◽  
Retinoic Acid Receptor ◽  
Rat Tissues ◽  
Mrna Levels ◽  
Acid Receptor ◽  
Beta Gene

We have investigated the effects of retinoids, vitamin D and thyroid hormone on the levels of retinoic acid receptor (RAR)alpha, RAR beta and RAR gamma mRNAs in intact animals. Although vitamin A deficiency caused no significant changes in the levels of RAR alpha and RAR gamma mRNAs, the level of RAR beta transcripts was greatly decreased in various tissues of vitamin A-deficient rats, but was restored rapidly to a normal level after administration of retinoic acid. Retinol also restored the RAR beta mRNA level, but the magnitude and kinetics of the induction differed from those by retinoic acid. The use of specific inhibitors demonstrated that this autoregulation of RAR beta gene expression in vivo occurred at the transcriptional level. In addition, from these results it was postulated that the maintenance of the normal RAR beta mRNA levels seemed to require a threshold serum retinol concentration (about 25 micrograms/dl). Moreover, we found that administration of retinol and retinoic acid to normal rats caused the overexpression of RAR beta transcripts (2-15-fold) when compared with the control levels of RAR beta mRNA, although the levels of RAR alpha and RAR gamma mRNAs were not affected. Vitamin D and thyroid hormone did not modulate the levels of RAR transcripts. These findings clearly indicate the specific ligand regulation of RAR beta gene expression in intact animals. The altered levels of RAR beta according to retinoid status may affect retinoid-inducible gene expression.

Sign in / Sign up

Export Citation Format

Share Document