scholarly journals Retinoic Acid Receptors and the Control of Positional Information in the Regenerating Axolotl Limb

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2174
Author(s):  
Trey Polvadore ◽  
Malcolm Maden
Keyword(s):  
Retinoic Acid ◽  
Acid Metabolism ◽  
Retinoic Acid Receptor ◽  
Limb Regeneration ◽  
Positional Information ◽  
Matrix Compartment ◽  
Selective Agonists ◽  
Upregulated Genes ◽  
Acid Administration ◽  
Target Effects

We know little about the control of positional information (PI) during axolotl limb regeneration, which ensures that the limb regenerates exactly what was amputated, and the work reported here investigates this phenomenon. Retinoic acid administration changes the PI in a proximal direction so that a complete limb can be regenerated from a hand. Rather than identifying all the genes altered by RA treatment of the limb, we have eliminated many off-target effects by using retinoic acid receptor selective agonists. We firstly identify the receptor involved in this respecification process as RARα and secondly, identify the genes involved by RNA sequencing of the RARα-treated blastemal mesenchyme. We find 1177 upregulated genes and 1403 downregulated genes, which could be identified using the axolotl genome. These include several genes known to be involved in retinoic acid metabolism and in patterning. Since positional information is thought to be a property of the cell surface of blastemal cells when we examine our dataset with an emphasis on this aspect, we find the top canonical pathway is integrin signaling. In the extracellular matrix compartment, we find a MMP and several collagens are upregulated; several cell membrane genes and secretory factors are also upregulated. This provides data for future testing of the function of these candidates in the control of PI during limb regeneration.

Delta retinoic acid receptor isoform δ1 is distinguished by its exceptional N-terminal sequence and abundance in the limb regeneration blastema

1993 ◽  
Vol 40 (1-2) ◽  
pp. 99-112 ◽  
Author(s):  
Clifton W. Ragsdale ◽  
Phillip B. Gates ◽  
David S. Hill ◽  
Jeremy P. Brockes
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Limb Regeneration ◽  
Terminal Sequence ◽  
Acid Receptor ◽  
Regeneration Blastema

scholarly journals Effect of Specific Retinoic Acid Receptor Agonists on Noise-Induced Hearing Loss

2019 ◽  
Vol 16 (18) ◽  
pp. 3428 ◽  
Author(s):  
Sang Hyun Kwak ◽  
Gi-Sung Nam ◽  
Seong Hoon Bae ◽  
Jinsei Jung
Keyword(s):  
Hearing Loss ◽  
Retinoic Acid ◽  
Noise Exposure ◽  
Retinoic Acid Receptor ◽  
Protective Effects ◽  
Noise Induced Hearing Loss ◽  
Acid Receptor ◽  
Significant Difference ◽  
Brainstem Response ◽  
Selective Agonists

Noise is one of the most common causes of hearing loss in industrial countries. There are many studies about chemical agents to prevent noise-induced hearing loss (NIHL). However, there is no commercially available drug yet. Retinoic acid is an active metabolite of Vitamin A; it has an anti-apoptic role in NIHL. This study aims to verify the differences among selective agonists of retinoic acid receptors (RARs) in NIHL. All-trans retinoic acid (ATRA), AM80 (selective retinoic acid receptor α agonist), AC261066 (Selective retinoic acid receptor β1 agonist), and CD1530 (Selective retinoic acid λ agonist) were injected to 6–7 weeks old CJ5BL/6 mice before noise (110 dB for 3 h) exposure. In the auditory brainstem response test pre-, post 1, 3, and 7 days after noise exposure, not only ATRA but all kinds of selective RAR agonists showed protective effects in hearing threshold and wave I amplitude. Though there was no significant difference in the level of protective effects between agonists, α agonist showed the most prominent effect in preserving hearing function as well as outer hair cells after noise exposure. In conclusion, selective agonists of RAR demonstrate comparable protective effects against NIHL to retinoic acid. Given that these selective RAR agonists have less side effects than retinoic acid, they may be promising potential drugs against NIHL.

Effects of Retinoic Acid Receptor–Selective Agonists on Human Nasal Epithelial Cell Differentiation

2001 ◽  
Vol 25 (6) ◽  
pp. 744-750 ◽  
Author(s):  
Karine Million ◽  
Frédéric Tournier ◽  
Odile Houcine ◽  
Philippe Ancian ◽  
Uwe Reichert ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Differentiation ◽  
Epithelial Cell ◽  
Retinoic Acid Receptor ◽  
Nasal Epithelial Cell ◽  
Human Nasal Epithelial Cell ◽  
Acid Receptor ◽  
Epithelial Cell Differentiation ◽  
Selective Agonists

Identification of a novel isoform of the retinoic acid receptor gamma expressed in the mouse embryo

1990 ◽  
Vol 10 (5) ◽  
pp. 2335-2340
Author(s):  
V Giguère ◽  
M Shago ◽  
R Zirngibl ◽  
P Tate ◽  
J Rossant ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Mouse Embryo ◽  
Retinoic Acid Receptor ◽  
Limb Bud ◽  
Retinoic Acid Receptors ◽  
Amino Terminus ◽  
Mammalian Development ◽  
Teratogenic Effects ◽  
Pregnant Mice ◽  
Acid Administration

Retinoic acid is known to have profound effects on developmental processes. It has been implicated as a putative morphogen in the developing chick limb bud and regenerating amphibian limb blastema and has been demonstrated to have powerful teratogenic effects in mammals, including humans. Recently, three specific retinoic acid receptors (RARs), RAR alpha, -beta, and -gamma, were identified and shown to be members of the steroid receptor superfamily. We report the identification of a novel RAR gamma isoform, mRAR gamma B, which differs from the previously described mouse RAR gamma at its amino terminus. In addition, we show that both RAR gamma isoforms are expressed maximally at midgestation in structures known to be affected adversely by retinoic acid administration to pregnant mice. Multiple RAR isoforms, each of which may play a unique or combinatorial role as a regulator of mammalian development, are thus expressed in the mouse embryo.

scholarly journals Identification of a novel isoform of the retinoic acid receptor gamma expressed in the mouse embryo.

1990 ◽  
Vol 10 (5) ◽  
pp. 2335-2340 ◽  
Author(s):  
V Giguère ◽  
M Shago ◽  
R Zirngibl ◽  
P Tate ◽  
J Rossant ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Mouse Embryo ◽  
Retinoic Acid Receptor ◽  
Limb Bud ◽  
Retinoic Acid Receptors ◽  
Amino Terminus ◽  
Mammalian Development ◽  
Teratogenic Effects ◽  
Pregnant Mice ◽  
Acid Administration

Retinoic acid is known to have profound effects on developmental processes. It has been implicated as a putative morphogen in the developing chick limb bud and regenerating amphibian limb blastema and has been demonstrated to have powerful teratogenic effects in mammals, including humans. Recently, three specific retinoic acid receptors (RARs), RAR alpha, -beta, and -gamma, were identified and shown to be members of the steroid receptor superfamily. We report the identification of a novel RAR gamma isoform, mRAR gamma B, which differs from the previously described mouse RAR gamma at its amino terminus. In addition, we show that both RAR gamma isoforms are expressed maximally at midgestation in structures known to be affected adversely by retinoic acid administration to pregnant mice. Multiple RAR isoforms, each of which may play a unique or combinatorial role as a regulator of mammalian development, are thus expressed in the mouse embryo.

scholarly journals Selective Agonists of Nuclear Retinoic Acid Receptor Gamma Inhibit Growth of HCS‐2/8 Chondrosarcoma Cells

2019 ◽  
Vol 38 (5) ◽  
pp. 1045-1051
Author(s):  
William P. Shield ◽  
Ashley Cellini ◽  
Hongying Tian ◽  
Kim Wilson ◽  
Yang Dan ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Acid Receptor ◽  
Selective Agonists

Synthetic Retinoids Beyond Cancer Therapy

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Lorraine J. Gudas
Keyword(s):  
Retinoic Acid ◽  
Skin Diseases ◽  
Retinoic Acid Receptor ◽  
Multiple Roles ◽  
Annual Review ◽  
Publication Date ◽  
All Trans Retinoic Acid ◽  
Selective Agonists ◽  
Pharmaceutical Properties ◽  
New Research

While the uses of retinoids for cancer treatment continue to evolve, this review focuses on other therapeutic areas in which retinoids [retinol (vitamin A), all- trans retinoic acid (RA), and synthetic retinoic acid receptor (RAR)α-, β-, and γ-selective agonists] are being used and on promising new research that suggests additional uses for retinoids for the treatment of disorders of the kidneys, skeletal muscles, heart, pancreas, liver, nervous system, skin, and other organs. The most mature area, in terms of US Food and Drug Administration–approved, RAR-selective agonists, is for treatment of various skin diseases. Synthetic retinoid agonists have major advantages over endogenous RAR agonists such as RA. Because they act through a specific RAR, side effects may be minimized, and synthetic retinoids often have better pharmaceutical properties than does RA. Based on our increasing knowledge of the multiple roles of retinoids in development, epigenetic regulation, and tissue repair, other exciting therapeutic areas are emerging. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals MouseP450RAI(CYP26) Expression and Retinoic Acid-inducible Retinoic Acid Metabolism in F9 Cells Are Regulated by Retinoic Acid Receptor γ and Retinoid X Receptor α

1998 ◽  
Vol 273 (4) ◽  
pp. 2409-2415 ◽  
Author(s):  
Suzan S. Abu-Abed ◽  
Barbara R. Beckett ◽  
Hideki Chiba ◽  
James V. Chithalen ◽  
Glenville Jones ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acid Metabolism ◽  
Retinoic Acid Receptor ◽  
Retinoid X Receptor ◽  
F9 Cells ◽  
Acid Receptor

scholarly journals Spermatogonia Differentiation Requires Retinoic Acid Receptor γ

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 438-449 ◽  
Author(s):  
Aurore Gely-Pernot ◽  
Mathilde Raverdeau ◽  
Catherine Célébi ◽  
Christine Dennefeld ◽  
Betty Feret ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Nuclear Receptor ◽  
Sertoli Cells ◽  
Retinoic Acid Receptor ◽  
Vitamin A Deficiency ◽  
Seminiferous Tubules ◽  
Wild Type ◽  
Differentiation Markers ◽  
Selective Agonists

Vitamin A is instrumental to mammalian reproduction. Its metabolite, retinoic acid (RA), acts in a hormone-like manner through binding to and activating three nuclear receptor isotypes, RA receptor (RAR)α (RARA), RARβ, and RARγ (RARG). Here, we show that 1) RARG is expressed by A aligned (Aal) spermatogonia, as well as during the transition from Aal to A1 spermatogonia, which is known to require RA; and 2) ablation of Rarg, either in the whole mouse or specifically in spermatogonia, does not affect meiosis and spermiogenesis but impairs the Aal to A1 transition in the course of some of the seminiferous epithelium cycles. Upon ageing, this phenomenon yields seminiferous tubules containing only spermatogonia and Sertoli cells. Altogether, our findings indicate that RARG cell-autonomously transduces, in undifferentiated spermatogonia of adult testes, a RA signal critical for spermatogenesis. During the prepubertal spermatogenic wave, the loss of RARG function can however be compensated by RARA, as indicated by the normal timing of appearance of meiotic cells in Rarg-null testes. Accordingly, RARG- and RARA-selective agonists are both able to stimulate Stra8 expression in wild-type prepubertal testes. Interestingly, inactivation of Rarg does not impair expression of the spermatogonia differentiation markers Kit and Stra8, contrary to vitamin A deficiency. This latter observation supports the notion that the RA-signaling pathway previously shown to operate in Sertoli cells also participates in spermatogonia differentiation.

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