scholarly journals Role of Vitamin A/Retinoic Acid in Regulation of Embryonic and Adult Hematopoiesis

Nutrients ◽  
2017 ◽  
Vol 9 (2) ◽  
pp. 159 ◽  
Author(s):  
Ana Cañete ◽  
Elena Cano ◽  
Ramón Muñoz-Chápuli ◽  
Rita Carmona
Keyword(s):  
Retinoic Acid ◽  
Vitamin A

scholarly journals The role of retinoic acid in embryonic and post-embryonic development

2000 ◽  
Vol 59 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Malcolm Maden
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Embryonic Development ◽  
Cell Regeneration ◽  
Spinal Cord Regeneration ◽  
Experimental Paradigm ◽  
Hair Cell Regeneration ◽  
X Receptors ◽  
Lung Regeneration

Retinoic acid (RA) is the bioactive metabolite of vitamin A (retinol) which acts on cells to establish or change the pattern of gene activity. Retinol is converted to RA by the action of two types of enzyme, retinol dehydrogenases and retinal dehydrogenases. In the nucleus RA acts as a ligand to activate two families of transcription factors, the RA receptors (RAR) and the retinoid X receptors (RXR) which heterodimerize and bind to the upstream sequences of RA-responsive genes. Thus, in addition to the well-established experimental paradigm of depriving animals of vitamin A to determine the role of RA in embryonic and post-embryonic development, molecular biology has provided us with two additional methodologies: knockout the enzymes or the RAR and RXR in the mouse embryo. The distribution of the enzymes and receptors, and recent experiments to determine the endogenous distribution of RA in the embryo are described here, as well as the effects on the embryo of knocking out the enzymes and receptors. In addition, recent studies using the classical vitamin A-deprivation technique are described, as they have provided novel insights into the regions of the embryo which crucially require RA, and the gene pathways involved in their development. Finally, the post-embryonic or regenerating systems in which RA plays a part are described, i.e. the regenerating limb, lung regeneration, hair cell regeneration in the ear and spinal cord regeneration in the adult.

scholarly journals Vitamin A, Cancer Treatment and Prevention: The New Role of Cellular Retinol Binding Proteins

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Elena Doldo ◽  
Gaetana Costanza ◽  
Sara Agostinelli ◽  
Chiara Tarquini ◽  
Amedeo Ferlosio ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Cancer Progression ◽  
Binding Proteins ◽  
Bone Growth ◽  
Animal Origin ◽  
Ovarian Cancer Cells ◽  
Tissue Remodelling ◽  
Wide Range

Retinol and vitamin A derivatives influence cell differentiation, proliferation, and apoptosis and play an important physiologic role in a wide range of biological processes. Retinol is obtained from foods of animal origin. Retinol derivatives are fundamental for vision, while retinoic acid is essential for skin and bone growth. Intracellular retinoid bioavailability is regulated by the presence of specific cytoplasmic retinol and retinoic acid binding proteins (CRBPs and CRABPs). CRBP-1, the most diffuse CRBP isoform, is a small 15 KDa cytosolic protein widely expressed and evolutionarily conserved in many tissues. CRBP-1 acts as chaperone and regulates the uptake, subsequent esterification, and bioavailability of retinol. CRBP-1 plays a major role in wound healing and arterial tissue remodelling processes. In the last years, the role of CRBP-1-related retinoid signalling during cancer progression became object of several studies. CRBP-1 downregulation associates with a more malignant phenotype in breast, ovarian, and nasopharyngeal cancers. Reexpression of CRBP-1 increased retinol sensitivity and reduced viability of ovarian cancer cellsin vitro. Further studies are needed to explore new therapeutic strategies aimed at restoring CRBP-1-mediated intracellular retinol trafficking and the meaning of CRBP-1 expression in cancer patients’ screening for a more personalized and efficacy retinoid therapy.

scholarly journals Role of Vitamin A in Mammary Gland Development and Lactation

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 80 ◽  
Author(s):  
M. Teresa Cabezuelo ◽  
Rosa Zaragozá ◽  
Teresa Barber ◽  
Juan R. Viña
Keyword(s):  
Retinoic Acid ◽  
Mammary Gland ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Retinoid Signaling ◽  
Nutritional Problem ◽  
Pregnancy And Lactation ◽  
Gland Development

Vitamin A (all-trans-retinol), its active derivatives retinal and retinoic acid, and their synthetic analogues constitute the group of retinoids. It is obtained from diet either as preformed vitamin A or as carotenoids. Retinal plays a biological role in vision, but most of the effects of vitamin A are exerted by retinoic acid, which binds to nuclear receptors and regulates gene transcription. Vitamin A deficiency is an important nutritional problem, particularly in the developing world. Retinol and carotenoids from diet during pregnancy and lactation influence their concentration in breast milk, which is important in the long term, not only for the offspring, but also for maternal health. In this study, we review the role of vitamin A in mammary gland metabolism, where retinoid signaling is required not only for morphogenesis and development of the gland and for adequate milk production, but also during the weaning process, when epithelial cell death is coupled with tissue remodeling.

scholarly journals A Critical Role for the Retinoic Acid Signaling Pathway in the Pathophysiology of Gastrointestinal Graft-Versus-Host Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 341-341
Author(s):  
Xiao Chen ◽  
Joseph Dodge ◽  
William R. Drobyski
Keyword(s):  
T Cells ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Graft Versus Host Disease ◽  
Th17 Cells ◽  
Transplant Recipients ◽  
Graft Versus Host ◽  
Target Organs ◽  
Donor T Cells

Abstract Abstract 341 Damage to the gastrointestinal tract during graft-versus-host disease (GVHD) is one of the major causes of morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. However, the molecular mechanism(s) responsible for colonic GVHD induction remain obscure. All-trans retinoic acid (RA) is an active metabolite of vitamin A and has recently emerged as a critical regulator of gut immunity. We hypothesized that administration of RA might be a strategy to reduce inflammatory responses during GVHD, particularly within the colon microenvironment. In a B6→Balb/c MHC-mismatched murine allogeneic bone marrow transplantation (BMT) model, we found unexpectedly that exposure of recipient mice to exogenous RA resulted in significantly accelerated GVHD-associated mortality compared with DMSO-treated animals (p<0.0001). Histological examination of GVHD target organs 5 weeks after transplantation revealed a significant increase in pathologic damage in the colons of RA-treated mice compared with DMSO-treated animals (9.7 ± 0.8 versus 3.3 ± 0.9, p<0.001), whereas there was no significant difference in pathology scores in either the lung or liver. RA treatment resulted in significantly increased expression of the gut-homing molecules, CCR9 and α4β7, on donor T cells in mesenteric lymph nodes early after BMT. Notably, expression of other chemokine receptors that have been implicated in GVHD pathogenesis, such as CCR5, CXCR3, and CCR10, was not affected by RA treatment, demonstrating a selective role of RA in imprinting gut-homing donor T cells. Examination of GVHD target organs three weeks after transplantation revealed a significant increase (eight-fold) in the absolute numbers of both CD4+IFN-γ+ (TH1) and CD4+IL-17+ (TH17) cells in the colon of RA-treated mice versus DMSO-treated animals, whereas there were no statistical differences in TH1 or TH17 cells in the spleen, liver and lung. There was also a significant increase in the absolute number of regulatory T cells (Tregs) in the colon of RA-treated mice. However, the increase in Tregs was noted to be more modest (three-fold) than was observed for TH1 and TH17 cells, suggesting a pro-inflammatory role of RA. To further confirm a role for RA in imprinting gut-homing donor T cells during GVHD, we generated vitamin A-deficient mice and employed them as recipients. Depletion of RA in recipient mice by vitamin A deprivation resulted in a dramatic reduction of gut homing molecule expression on donor T cells after allogeneic BMT. Retinoic acid receptor-α (RAR-α) signaling appears to be critical in mediating the effects of RA on alloreactive T cells. In mixed lymphocyte culture, when B6 T cells were stimulated with Balb/c dendritic cells, the presence of an RAR-α agonist was able to significantly enhance the expression of gut-homing molecules on T cells. In contrast, the addition of a selective RAR-α antagonist abolished the effects of RA on T cells. We then measured endogenous RA levels in the colons of mice undergoing either syngeneic or allogeneic BMT by mass spectrometry. These studies revealed that RA was significantly increased in the colon tissue of allogeneic transplant recipients compared with syngeneic transplant recipients early after BMT (day 7). In addition, Real-Time q-PCR analysis revealed a mean 3.5-fold increase in RAR-α expression in purified donor splenic CD4+ T cells 4 days post transplantation when compared to purified naïve CD4+ T cells obtained from original donor animals. Finally, we examined the ability of RAR-α-deficient T cells to cause GVHD. We found that recipients of RAR-α-deficient marrow grafts had significantly decreased GVHD-associated mortality when compared with the recipients of wild type T cells (93% versus 36% at day 90, p=0.002). Histological examination of GVHD target organs on days 10–12 after transplantation revealed a significant reduction in pathologic damage in the colon of mice that received RAR-α-deficient T cells compared with control mice (7.3 ± 2.5 versus 0.8 ± 1.0, p<0.01). In summary, we have identified RA as a novel and critical molecule in the induction of gastrointestinal GVHD. These findings provide evidence that blockade of the RA signaling pathway may represent a novel strategy to mitigate the severity of colonic GVHD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Role and Mechanism of Vitamin A Metabolism in the Pathophysiology of Parkinson’s Disease

2021 ◽  
pp. 1-22
Author(s):  
Anaıs Marie ◽  
Morgane Darricau ◽  
Katia Touyarot ◽  
Louise C. Parr-Brownlie ◽  
Clémentine Bosch-Bouju
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Dopaminergic Neurons ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Vitamin A Metabolism ◽  
Health And Wellbeing

Evidence shows that altered retinoic acid signaling may contribute to the pathogenesis and pathophysiology of Parkinson’s disease (PD). Retinoic acid is the bioactive derivative of the lipophilic vitamin A. Vitamin A is involved in several important homeostatic processes, such as cell differentiation, antioxidant activity, inflammation and neuronal plasticity. The role of vitamin A and its derivatives in the pathogenesis and pathophysiology of neurodegenerative diseases, and their potential as therapeutics, has drawn attention for more than 10 years. However, the literature sits in disparate fields. Vitamin A could act at the crossroad of multiple environmental and genetic factors of PD. The purpose of this review is to outline what is known about the role of vitamin A metabolism in the pathogenesis and pathophysiology of PD. We examine key biological systems and mechanisms that are under the control of vitamin A and its derivatives, which are (or could be) exploited for therapeutic potential in PD: the survival of dopaminergic neurons, oxidative stress, neuroinflammation, circadian rhythms, homeostasis of the enteric nervous system, and hormonal systems. We focus on the pivotal role of ALDH1A1, an enzyme expressed by dopaminergic neurons for the detoxification of these neurons, which is under the control of retinoic acid. By providing an integrated summary, this review will guide future studies on the potential role of vitamin A in the management of symptoms, health and wellbeing for PD patients.

scholarly journals Vitamin A and immune regulation: Role of retinoic acid in gut-associated dendritic cell education, immune protection and tolerance

2012 ◽  
Vol 33 (1) ◽  
pp. 63-76 ◽  
Author(s):  
Barbara Cassani ◽  
Eduardo J. Villablanca ◽  
Jaime De Calisto ◽  
Sen Wang ◽  
J. Rodrigo Mora
Keyword(s):  
Retinoic Acid ◽  
Dendritic Cell ◽  
Vitamin A ◽  
Immune Regulation ◽  
Immune Protection
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