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Retinoic acid receptors

Shigeki Fujiwara, Cristian Cañestro
Reporter analyses of Hox1 and Brachyury (Bra) genes have revealed examples of redundant enhancers that provide regulatory robustness. Retinoic acid (RA) activates through an RA-response element the transcription of Hox1 in the nerve cord of the ascidian Ciona intestinalis. We also found a weak RA-independent neural enhancer within the second intron of Hox1. The Hox1 gene in the larvacean Oikopleura dioica is also expressed in the nerve cord. The O. dioica genome, however, does not contain the RA receptor-encoding gene, and the expression of Hox1 has become independent of RA...
2018: Advances in Experimental Medicine and Biology
Hironori Yoshino, Miyu Iwabuchi, Yuka Kazama, Maho Furukawa, Ikuo Kashiwakura
Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns and induce antiviral immune responses. Recent studies have demonstrated that RLR activation induces antitumor immunity and cytotoxicity against different types of cancer, including lung cancer. However a previous report has demonstrated that ionizing radiation exerts a limited effect on RLR in human monocytic cell-derived macrophages, suggesting that RLR agonists may be used as effective immunostimulants during radiation therapy...
April 2018: Oncology Letters
Yiran Ao, Qin Zhao, Kai Yang, Gang Zheng, Xiaoqing Lv, Xiaoli Su
Clock genes are the core of the circadian rhythms in the human body and are important in regulating normal physiological functions. To date, research has indicated that the clock gene, period circadian clock 2 ( PER2 ), is downregulated in numerous types of cancer, and that it is associated with cancer occurrence and progression via the regulation of various downstream cell cycle genes. However, it remains unclear whether the decreased expression of PER2 influences the expression of other clock genes in cancer cells...
April 2018: Oncology Letters
Can Chen, Xilian Huang, Kaile Wang, Kuang Chen, Danquan Gao, Shenxian Qian
Acute promyelocytic leukemia (APL) is a rare leukemia characterized by the balanced reciprocal translocation between the promyelocytic leukemia gene on chromosome 15 and the retinoic acid receptor α (RARα) gene on chromosome 17, and accounts for 10-15% of newly diagnosed acute myeloid leukemia each year. The combined use of all-trans retinoic acid and arsenic trioxide (ATO) as primary therapy has markedly improved the survival rate of patients with APL. Mortality in the first 30 days following therapy remains a major contribution to treatment failure...
April 2018: Oncology Letters
Guohong Wen, Huadong Wang, Zhaohui Zhong
BACKGROUND: Oral tumor is a heterogeneous group of tumors, in which it has several different histopathological and molecular features. Recently, genetic and epigenetic alterations are often detected in the development of oral cancer. Gene promoter hypermethylation leads to the silencing of cancer related genes without changes of genes sequence. To clarify the effect of RAS association domain family protein 1a (RASSF1A), retinoic acid receptor beta (RARβ), and E-cadherin (CDH1) promoter hypermethylation on the risk of oral cancer, we performed this meta-analysis...
March 2018: Medicine (Baltimore)
Constance A Mitchell, Subham Dasgupta, Sharon Zhang, Heather M Stapleton, David C Volz
Triphenyl phosphate (TPHP) is an unsubstituted aryl phosphate ester used as a flame retardant and plasticizer within the United States. Using zebrafish as a model, the objectives of this study were to rely on 1) mRNA-sequencing to uncover pathways disrupted following embryonic TPHP exposure and 2) high-content screening to identify nuclear receptor ligands that enhance or mitigate TPHP-induced cardiotoxicity. Based on mRNA-sequencing, TPHP exposure from 24 to 72 h post fertilization (hpf) resulted in a concentration-dependent increase in the number of transcripts significantly affected at 72 hpf, and pathway analysis revealed that five out of nine nuclear receptor pathways were associated with the retinoid X receptor (RXR)...
February 24, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Fangjia Lu, Qingyang Liu
The impact of unrhythmic circadian clock on obesity has started to be increasingly appreciated nowadays. Recently it was discovered that interaction between intestinal microbiota and unrhythmic circadian clock plays a key role in such a process. It involves relaying signals from microbiota through dendritic cells to group 3 innate lymphoid cells in the intestine and in the end impacting some of the key transcription factors of circadian clock. Breaking such a signal relay may prove to be an effective way reducing unrhythmic circadian clock-induced obesity...
April 2018: Medical Hypotheses
Danyang Shen, Xiaoming Yu, Yan Wu, Yuanlei Chen, Gonghui Li, Feng Cheng, Liqun Xia
Retinoic acid X receptors play key roles in tumor cell proliferation, differentiation, apoptosis and angiogenesis via transcriptional regulation. Bexarotene is a specific RXRs agonist which has been granted by FDA approval for the clinical treatment of cutaneous T cell lymphoma (CTCL). Its cancer prevention and treatment potentials in various tumors have been under investigation over the past decade. Areas covered: This review summarizes the efficacy and underlying mechanisms of bexarotene for the treatment of multiple cancers based on the launched clinical trials as well as the basic studies...
March 9, 2018: Expert Review of Anticancer Therapy
Anna Ashton, Patrick N Stoney, Jemma Ransom, Peter McCaffery
Vitamin A is important for the circadian timing system; deficiency disrupts daily rhythms in activity and clock gene expression, and reduces the nocturnal peak in melatonin in the pineal gland. However, it is currently unknown how these effects are mediated. Vitamin A primarily acts via the active metabolite, retinoic acid (RA), a transcriptional regulator with emerging non-genomic activities. We investigated whether RA is subject to diurnal variation in synthesis and signaling in the rat pineal gland. Its involvement in two key molecular rhythms in this gland was also examined: kinase activation and induction of Aanat, which encodes the rhythm-generating melatonin synthetic enzyme...
March 8, 2018: Molecular Neurobiology
Qing Mu, Weidong Yu, Shuying Zheng, Hongxia Shi, Mei Li, Jie Sun, Di Wang, Xiaoli Hou, Ling Liu, Xinjuan Wang, Zhuran Zhao, Rong Liang, Xue Zhang, Wei Dong, Chaomei Zeng, Jingzhu Guo
Vitamin A deficiency and mitochondrial dysfunction are both associated with neural differentiation-related disorders, such as Alzheimer's disease (AD) and Down syndrome (DS). The mechanism of vitamin A-induced neural differentiation and the notion that vitamin A can regulate the morphology and function of mitochondria in its induction of neural differentiation through the RIP140/PGC-1α axis are unclear. The aim of this study was to investigate the roles and underlying mechanisms of RIP140/PGC-1α axis in vitamin A-induced neural differentiation...
March 7, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Liang Yi, Dan Sun, Qian Han, Zhonghui Liu, Zeng Zeng, Yanping Wu, Xiaoyu Chai, Xinmin Liu
Immunotherapy is considered one of the most promising treatments for lung cancer. The cell signalling molecules melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene I protein (RIG‑I) are essential receptors that recognise intracellular pathogen-associated nucleic acids, whereas interferon regulatory factor 3 (IRF3) controls the expression of innate immunity-associated genes in macrophages. However, the innate immune response to polyinosinic:polycytidylic acid [Poly(I:C)] in lung cancer remains to be elucidated...
March 5, 2018: International Journal of Oncology
Maryam Majd, Aref Hosseini, Kamran Ghaedi, Abbas Kiani-Esfahani, Somayeh Tanhaei, Hanieh Shiralian-Esfahani, Seyed Yahya Rahnamaee, Seyed Javad Mowla, Mohammad Hossein Nasr-Esfahani
Objectives: Multiple sclerosis (MS) is considered as a chronic type of an inflammatory disease characterized by loss of myelin of CNS. Recent evidence indicates that Interleukin 17 (IL-17)-producing T helper cells (Th17 cells) population are increased and regulatory T cells (Treg cells) are decreased in MS. Despite extensive research in understanding the mechanism of Th17 and Treg differentiation, the role of microRNAs in MS is not completely understood. Thereby, as a step closer, we analyzed the expression profile of miR-9-5p and miR-106a-5p, and protein level of retinoic acid receptor (RAR)-related orphan receptor C ( RORC ; Th17 master transcription factor) as direct target of miR-106a-5p and forkhead box P3 ( FOXP3 ; Treg master transcription factor) as indirect target of miR-9-5p in CD4+ T cells in two groups of relapsing and remitting in our relapsing-remitting MS (RR-MS) patients...
March 2018: Iranian Journal of Basic Medical Sciences
Adam M Reitzel, Jason Macrander, Daniel Mane-Padros, Bin Fang, Frances M Sladek, Ann M Tarrant
Nuclear receptors are a superfamily of transcription factors restricted to animals. These transcription factors regulate a wide variety of genes with diverse roles in cellular homeostasis, development, and physiology. The origin and specificity of ligand binding within lineages of nuclear receptors (e.g., subfamilies) continues to be a focus of investigation geared toward understanding how the functions of these proteins were shaped over evolutionary history. Among early-diverging animal lineages, the retinoid X receptor (RXR) is first detected in the placozoan, Trichoplax adhaerens...
March 3, 2018: Journal of Steroid Biochemistry and Molecular Biology
Mitsunori Kono, Atsuko Ochida, Tsuneo Oda, Takashi Imada, Yoshihiro Banno, Naohiro Taya, Shinichi Masada, Tetsuji Kawamoto, Kazuko Yonemori, Yoshi Nara, Yoshiyuki Fukase, Tomoya Yukawa, Hidekazu Tokuhara, Robert Skene, Bi-Ching Sang, Isaac D Hoffman, Gyorgy P Snell, Keiko Uga, Akira Shibata, Keiko Igaki, Yoshiki Nakamura, Hideyuki Nakagawa, Noboru Tsuchimori, Masashi Yamasaki, Junya Shirai, Satoshi Yamamoto
A series of tetrahydronaphthyridine derivatives as novel RORγt inverse agonists were designed and synthesized. We reduced the lipophilicity of tetrahydroisoquinoline compound 1 by replacement of the trimethylsilyl group and SBDD-guided scaffold exchange, which successfully afforded compound 7 with a lower logD value and tolerable in vitro activity. Consideration of LLE values in the subsequent optimization of the carboxylate tether led to the discovery of [cis-3-({(5R)-5-[(7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)carbamoyl]-2-methoxy-7,8-dihydro-1,6-naphthyridin-6(5H)-yl}carbonyl)cyclobutyl]acetic acid, TAK-828F (10), which showed potent RORγt inverse agonistic activity, excellent selectivity against other ROR isoforms and nuclear receptors, and a good pharmacokinetic profile...
March 6, 2018: Journal of Medicinal Chemistry
H de la Salle, C Angénieux, F Lanza, C Gachet
In a recent report published in J Thromb Haemost, Schwertz et al. [1] investigated whether all-trans retinoic acid (atRA) controls mRNA translation in human platelets. This report concluded that atRA negatively controls the interaction between retinoic acid receptor alpha protein (RARα) and specific mRNAs, thereby positively regulating their translation in platelets. These interesting observations could open a new field in the understanding of platelet biology and we would like to discuss four important aspects of this work that deserve to be considered in this perspective...
March 5, 2018: Journal of Thrombosis and Haemostasis: JTH
Chang H Kim
Lymphocytes, such as T cells, B cells, and innate lymphoid cells (ILCs), play central roles in regulating immune responses. Retinoic acids (RAs) are vitamin A metabolites, produced and metabolized by certain tissue cells and myeloid cells in a tissue-specific manner. It has been established that RAs induce gut-homing receptors on T cells, B cells, and ILCs. A mounting body of evidence indicates that RAs exert far-reaching effects on functional differentiation and fate of these lymphocytes. For example, RAs promote effector T cell maintenance, generation of induced gut-homing regulatory and effector T cell subsets, antibody production by B cells, and functional maturation of ILCs...
February 2018: Immune Network
Takahiro Hatayama, Ryosuke Segawa, Natsumi Mizuno, Sumiko Eguchi, Hiroshi Akamatsu, Misaki Fukuda, Fumihisa Nakata, Warren J Leonard, Masahiro Hiratsuka, Noriyasu Hirasawa
Many classical vaccines contain whole pathogens and, thus, may occasionally induce adverse effects, such as inflammation. Vaccines containing purified rAgs resolved this problem, but, owing to their low antigenicity, they require adjuvants. Recently, the use of several cytokines, including thymic stromal lymphopoietin (TSLP), has been proposed for this purpose. However, it is difficult to use cytokines as vaccine adjuvants in clinical practice. In this study, we examined the effects of all- trans retinoic acid (atRA) on TSLP production and Ag-induced Ab production...
March 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Tomio Matsumura, Shigeaki Hida, Masato Kitazawa, Chifumi Fujii, Akira Kobayashi, Michiko Takeoka, Shun-Ichiro Taniguchi, Shin-Ichi Miyagawa
Fascin1 is an actin-bundling protein involved in cancer cell migration and has recently been shown also to have roles in virus-mediated immune cell responses. Because viral infection has been shown to activate immune cells and to induce IFN-β expression in human cancer cells, we evaluated the effects of fascin1 on virus-dependent signaling via the membrane- and actin-associated protein retinoic acid-inducible gene I (RIG-I) in colon cancer cells. We knocked down fascin1 expression with shRNA retrovirally transduced into a DLD-1 colon cancer and L929 fibroblast-like cell lines and used luciferase reporter assays and co-immunoprecipitation to identify fascin1 targets...
March 1, 2018: Journal of Biological Chemistry
Mette Handberg-Thorsager, Juliana Gutierrez-Mazariegos, Stefan T Arold, Eswar Kumar Nadendla, Paola Y Bertucci, Pierre Germain, Pavel Tomançak, Keely Pierzchalski, Jace W Jones, Ricard Albalat, Maureen A Kane, William Bourguet, Vincent Laudet, Detlev Arendt, Michael Schubert
Retinoic acid (RA) is an important intercellular signaling molecule in vertebrate development, with a well-established role in the regulation of hox genes during hindbrain patterning and in neurogenesis. However, the evolutionary origin of the RA signaling pathway remains elusive. To elucidate the evolution of the RA signaling system, we characterized RA metabolism and signaling in the marine annelid Platynereis dumerilii , a powerful model for evolution, development, and neurobiology. Binding assays and crystal structure analyses show that the annelid retinoic acid receptor (RAR) binds RA and activates transcription just as vertebrate RARs, yet with a different ligand-binding pocket and lower binding affinity, suggesting a permissive rather than instructive role of RA signaling...
February 2018: Science Advances
Marine Lacomme, François Medevielle, Henri-Marc Bourbon, Elodie Thierion, Dirk-Jan Kleinjan, Mélanie Roussat, Fabienne Pituello, Sophie Bel-Vialar
Proper embryonic development relies on a tight control of spatial and temporal gene expression profiles in a highly regulated manner. One good example is the ON/OFF switching of the transcription factor PAX6 that governs important steps of neurogenesis. In the neural tube PAX6 expression is initiated in neural progenitors through the positive action of retinoic acid signaling and downregulated in neuronal precursors by the bHLH transcription factor NEUROG2. How these two regulatory inputs are integrated at the molecular level to properly fine tune temporal PAX6 expression is not known...
February 24, 2018: Developmental Biology
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