Gene expression following myocardial infarction in mice with Stimulated by retinoic acid gene 6 (Stra6) germline deletion, Vitamin A deficiency, and the combination of both
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE307187 | GEO | 2025/09/06
REPOSITORIES: GEO
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Project description:Vitamin A (retinol) is an essential precursor for the production of retinoic acid (RA), which in turn is a major regulator of gene expression, affecting cell differentiation throughout the body. Understanding how vitamin A nutritional status, as well as therapeutic retinoid treatment, regulates the expression of retinoid homeostatic genes is important for improving dietary recommendations and therapeutic strategies using retinoids. This study investigated genes central to processes of retinoid uptake and storage, release to plasma, and oxidation in the liver of rats under steady-state conditions after different exposures to dietary vitamin A (deficient, marginal, adequate and supplemented), and acutely after administration of a therapeutic dose of all-trans-RA. Over a very wide range of dietary vitamin A, lecithin:retinol acyltransferase (LRAT) as well as multiple cytochrome P450s (CYP26A1, CYP26B1, and CYP2C22) differed by diet and were highly correlated with one another and with vitamin A status assessed by liver retinol concentration (all correlations, P<0.05). After acute treatment with RA, the same genes were rapidly and concomitantly induced, preceding RARß, a classical direct target of RA. CYP26A1 mRNA exhibited the greatest dynamic range (change of log26 in 3 h). Moreover, CYP26A1 increased more rapidly in the liver of RA-primed rats than naïve rats. By in situ hybridization, CYP26A1 mRNA was strongly regulated within hepatocytes, closely resembling RBP4 in location. Overall, whether RA is produced endogenously from retinol or administered exogenously, changes in retinoid homeostatic gene expression simultaneously favor both retinol esterification and RA oxidation, with CYP26A1 exhibiting the greatest dynamic change.
2011-09-01 | GSE24104 | GEO
Project description:Vitamin A deficiency is detrimental to the visual system throughout the lifecycle. Abundant expression of the retinoid transporter STRA6 in the retinal pigment epithelium (RPE) and homeostatic blood levels of retinol binding protein ensure the eyes are adequately supplied with the nutrient. STRA6 deficiency interrupts the supply pathway, but vitamin A in chylomicrons compensates for its failure. However, dependency on the chylomicron delivery pathway makes the eyes of STRA6-deficient mice vulnerable to dietary vitamin A deprivation. How the eyes adapt to vitamin A status has not been studied in molecular detail, and therefore we used RNA-seq to focus on diet-induced changes. We observed that mild ocular vitamin A deficiency was linked to an increase in transcript abundance levels of genes coding for proteins of stress pathways and a decrease in levels of transcripts coding for proteins of pathways of visual sensitivity and perception. These changes correlate with a loss of visual sensitivity and accumulation of fluorescent debris in the retina. Additionally, severe vitamin A deficiency decreased the transcript levels of genes involved in cell adhesion, cell differentiation, and transport of small molecules pathways. This response correlated with alterations in epithelial cell morphology and a “leaky” RPE barrier. Together, our analyses of STRA6-deficient mice define adaptive responses associated with ocular vitamin A status and reveal a previously unknown role of STRA6 in the maintenance and functioning of the outer blood-retina barrier.
2023-06-07 | GSE219252 | GEO
Project description:Adenomyosis is an estrogen-dependent disease in which endometrial glands and stroma are pathologically demonstrated in the myometrium. Despite its prevalence and severity of symptoms, the precise etiology and physiopathology of adenomyosis is not well understood.Vitamin defciency increase in women with adenomyosis. Much less is known about the mechanism of their relationship. We found the retinol-binding protein receptor STRA6 upregulation in uterinespiral arteries from adenomyosis patients. The increased estrogen level promote the STRA6 expression, resulting the depressed Wnt/β-catenin signaling mediated by FASN/GSK-3β interaction. Overexpression of STRA6 induced epithelial to mesenchymal transition process. miR-1249-5p achieved its negative function by regulating the target gene through 3' UTR.The depletion of STRA6 in vivo alleviated the pathogenesis of adenomyosis. These results reveal a hitherto undesribed positive feedback loop between estrogen and STRA6 in adenomyosis pathogenesis. Components of vitamin A metabolism network have more complex activities than simply controlling or transferring VA compounds between different cells.
2023-09-06 | GSE242148 | GEO
Project description:Adenomyosis is an estrogen-dependent disease in which endometrial glands and stroma are pathologically demonstrated in the myometrium. Despite its prevalence and severity of symptoms, the precise etiology and physiopathology of adenomyosis is not well understood.Vitamin defciency increase in women with adenomyosis. Much less is known about the mechanism of their relationship. We found the retinol-binding protein receptor STRA6 upregulation in uterinespiral arteries from adenomyosis patients. The increased estrogen level promote the STRA6 expression, resulting the depressed Wnt/β-catenin signaling mediated by FASN/GSK-3β interaction. Overexpression of STRA6 induced epithelial to mesenchymal transition process. miR-1249-5p achieved its negative function by regulating the target gene through 3' UTR.The depletion of STRA6 in vivo alleviated the pathogenesis of adenomyosis. These results reveal a hitherto undesribed positive feedback loop between estrogen and STRA6 in adenomyosis pathogenesis. Components of vitamin A metabolism network have more complex activities than simply controlling or transferring VA compounds between different cells.
2023-09-06 | GSE242145 | GEO
Project description:We used microarrays to examine the temporal transcriptome changes of vitamin a deficient rats testes replenished with retinol 20-day old rats were put on a vitamin A deficient diet, after nine weeks the animals were treated with retinol for 0-(VAD), 4-, 8-, 24-hr to determine the global transcriptome changes induced by retinol replenishment of the vitmain A deficient testis
2009-02-27 | E-GEOD-14962 | biostudies-arrayexpress
Project description:Vitamin A is an exogenous micronutrient that is derived solely from diet and metabolized into retinoic acid, which acts as an antioxidant and transcriptional regulator. Here we show that obstruction of dietary Vitamin A drives mitochondrial and cell cycle dysfunction in MuSCs and myoblasts that mimics old age. The receptor for vitamin A derived retinol, Stra6, was found to be diminished with MuSC activation and in old age. The loss of Stra6 in myogenic progenitors resulted in accumulation of mitochondrial reactive oxygen species, as well as changes in mitochondrial morphology and respiration. Pharmacological targeting of Stra6 and retinoic acid signaling in myogenic progenitors and aged MuSCs reverted oxidative damage, enhanced mitochondrial function, and improved maintenance of quiescence. These results demonstrate that Vitamin A regulates mitochondria and metabolism in MuSCs to promote quiescence. These results highlight a unique mechanism connecting stem cell function with vitamin intake.
2024-06-03 | GSE268617 | GEO
Project description:Vitamin A is an exogenous micronutrient that is derived solely from diet and metabolized into retinoic acid, which acts as an antioxidant and transcriptional regulator. Here we show that obstruction of dietary Vitamin A drives mitochondrial and cell cycle dysfunction in MuSCs and myoblasts that mimics old age. The receptor for vitamin A derived retinol, Stra6, was found to be diminished with MuSC activation and in old age. The loss of Stra6 in myogenic progenitors resulted in accumulation of mitochondrial reactive oxygen species, as well as changes in mitochondrial morphology and respiration. Pharmacological targeting of Stra6 and retinoic acid signaling in myogenic progenitors and aged MuSCs reverted oxidative damage, enhanced mitochondrial function, and improved maintenance of quiescence. These results demonstrate that Vitamin A regulates mitochondria and metabolism in MuSCs to promote quiescence. These results highlight a unique mechanism connecting stem cell function with vitamin intake.
2024-06-03 | GSE268616 | GEO
Project description:Vitamin A (retinol) is an essential precursor for the production of retinoic acid (RA), which in turn is a major regulator of gene expression, affecting cell differentiation throughout the body. Understanding how vitamin A nutritional status, as well as therapeutic retinoid treatment, regulates the expression of retinoid homeostatic genes is important for improving dietary recommendations and therapeutic strategies using retinoids. This study investigated genes central to processes of retinoid uptake and storage, release to plasma, and oxidation in the liver of rats under steady-state conditions after different exposures to dietary vitamin A (deficient, marginal, adequate and supplemented), and acutely after administration of a therapeutic dose of all-trans-RA. Over a very wide range of dietary vitamin A, lecithin:retinol acyltransferase (LRAT) as well as multiple cytochrome P450s (CYP26A1, CYP26B1, and CYP2C22) differed by diet and were highly correlated with one another and with vitamin A status assessed by liver retinol concentration (all correlations, P<0.05). After acute treatment with RA, the same genes were rapidly and concomitantly induced, preceding RARß, a classical direct target of RA. CYP26A1 mRNA exhibited the greatest dynamic range (change of log26 in 3 h). Moreover, CYP26A1 increased more rapidly in the liver of RA-primed rats than naïve rats. By in situ hybridization, CYP26A1 mRNA was strongly regulated within hepatocytes, closely resembling RBP4 in location. Overall, whether RA is produced endogenously from retinol or administered exogenously, changes in retinoid homeostatic gene expression simultaneously favor both retinol esterification and RA oxidation, with CYP26A1 exhibiting the greatest dynamic change. All rats were housed in a room maintained at 22°C with a 12-h dark:light cycle, and food and water were freely available. For the Steady-State Vitamin A Study (experiment 1) and the Retinoic Acid 16-hour Kinetic Study (experiment 2), lactating female Sprague-Dawley rats with 12 female pups (purchased from Charles River Laboratories, Willmington, MA) were fed a vitamin A-deficient purified diet [AIN-93G diet, prepared by Research Diets, New Brunswick, NJ] to reduce the transfer of vitamin A in milk from mother to pups prior to the start of the study. For experiment 1, from weaning, the offspring were fed the same diet modified to contain vitamin A at one of four levels: 0 (vitamin A deficient), 0.4 mg retinol/kg diet (vitamin A marginal), 4 mg retinol/kg diet (vitamin A adequate control), or 100 mg retinol/kg diet (vitamin A supplemented). All rats were studied at 8 weeks of age. Rats were euthanized by carbon dioxide asphyxiation and blood and liver were collected rapidly and frozen in liquid nitrogen for storage at -80°C before analysis. In experiment 2, at 8 weeks of age female vitamin A-deficient rats were treated with ~100 ug of All-trans-Retinoic acid (at-RA) for 0 (vehicle only), 3, 6, 10 or 16 h (n=3-4/group). Tissues were collected and RNA was prepared in the same manner as in experiment 1. In the 90-minute "first pass" kinetic study (experiment 3), female rats were purchased at 6 weeks of age and fed a stock rodent diet. When the rats were 8 weeks old they were assigned to a control (naïve) group. Rats in the naive group received an equal amount of vehicle only (vegetable oil/5% ethanol). Food was removed immediately. Sixteen hours after priming, each rat was lightly anesthetized by isoflurane-oxygen inhalation and treated with ~25 ug all-trans-RA bound to albumin [10 ug RA per 100 g bo dy weight], injected into the exposed left common iliac vein. The incision was closed with a surgical staple. The rats were allowed to recover from the anesthesia. Rats were killed at 0 minute (vehicle injection), and 30, 60, and 90 min (n = 3/group) after injection of the RA test dose. Rats were euthanized by carbon dioxide asphyxiation and blood and liver were collected rapidly and frozen in liquid nitrogen for storage at -80°C before analysis. For experiment 1, five biological repeats were Vitamin A deficient, seven biological repeats were Vitamin A marginal, six biological repeats were Vitamin A adequate, and two biological repeats were Vitamin A supplemented. In experiment 2, three biological repeats were performed for each of the following treatments: untreated, at-RA for 3 hours, at-RA for 6 hours and at-RA for 16 hours. Four biological repeats were treated with at-RA for 10 hours. For experiment 3, two biological repeats were untreated and three biological repeats were performed for each of the following at-RA treatment times: 30, 60 and 90 minutes. A total of 47 samples were analyzed.
2011-08-31 | E-GEOD-24104 | biostudies-arrayexpress
Project description:Vitamin A deficiencies and insufficiencies affect hundreds of millions of people in both developing and developed countries. These individuals experience higher rates of mortality and increased morbidity during enteric and respiratory infections compared to those who are vitamin A sufficient. Previously, our laboratory has demonstrated that vitamin A-deficient (VAD) mice have significantly impaired virus-specific IgA and CD8+ T cell responses in the airways. Here we demonstrate that VAD mice experience enhanced cytokine/chemokine gene expression and release in the respiratory tract 10 days following virus infection compared to control vitamin A-sufficient animals. Cytokines/chemokines that are reproducibly upregulated at the gene expression and protein levels include IFNγ and IL-6. Despite previous indications that cytokine dysregulation in VAD animals might reflect low forkhead box (Fox)P3+ T cell frequencies, we found no reduction in FoxP3+ T cells in VAD respiratory tissues. As an alternative explanation for the high cytokine levels, we found that virus infection and viral antigen persistence were enhanced on day 10 post-infection in VAD animals compared to controls, and that respiratory tract tissues had an increased potential to activate virus-specific T cells. Results encourage cautious management of virus infections in patients with VAD; efforts to enhance FoxP3+ T cell frequencies and quell immune effectors might in some cases exacerbate disease if virus has not been cleared. We used microarrays to explore the gene expression profiles differentially expressed in nasal-associated lymph tissue (NALT) lymphocytes from vitamin A-sufficient and vitamin A-deficient mice following infection with Sendai virus.
2016-02-11 | E-GEOD-65805 | biostudies-arrayexpress
Project description:Purpose. Patients with diabetic retinopathy may experience severe vision loss due to macular edema and neovascularization secondary to vascular abnormalities. However, before these abnormalities become apparent, there are functional deficits in contrast sensitivity, color perception, and dark adaptation. The goals of this study are to evaluate early changes (up to 3 months) in retinal gene expression, selected visual cycle proteins, and optokinetic tracking (OKT) in streptozotocin (STZ)-induced diabetic rats.Methods. Retinal gene expression in diabetic Long Evans rats was measured by whole genome microarray 7 days, 4 weeks, and three months after onset of hyperglycemia. Select gene and protein changes were probed by PCR and immunohistochemistry respectively, and OKT thresholds were measured using a virtual optokinetics system. Results. Microarray analysis showed that the most consistently affected molecular and cellular functions were cell-to-cell signaling and interaction, cell death, cellular growth and proliferation, molecular transport, and cellular movement. Further analysis revealed reduced expression of several genes encoding visual cycle proteins including lecithin:retinol acyltransferase (LRAT), retinal pigment epithelium (RPE)-specific protein 65kDa (RPE65) and RPE retinal G protein coupled receptor (RGR). Immunohistochemistry revealed a decrease in RPE65 in the RPE layer of diabetic rats. These molecular changes occurred simultaneously with a decrease in OKT thresholds by 4 weeks of diabetes. Conclusions. The data presented here are further evidence that inner retinal cells are affected by hyperglycemia prior to vasculopathy suggesting that glial and neuronal dysfunction may underlie some of the early visual deficits in diabetics.
2011-10-31 | GSE28831 | GEO