In vitro gene signature of cultured adult keratinocytes stimulated by all trans retinoic acid (atRA) and/or Poly I:C
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PROVIDER: PRJNA527459 | ENA |
REPOSITORIES: ENA
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Project description:How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate entirely new hair follicles de novo following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor TLR3 to induce intrinsic retinoic acid (RA) synthesis in a gradient that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a novel stimulus for retinoic acid synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity. Hand keratinocytes were treated with atRA (0.1 uM) and/or Poly I:C (0.1 ug/ml). RNA was extracted and sent for microarray analysis
2019-05-22 | GSE128407 | GEO
Project description:All-trans retinoic acid (ATRA) is a potent retinoid, which has been used successfully in different clinical settings as a potential drug to treat COPD and emphysema. In alveolar macrophages, ATRA selectively down-regulates MMP-9 and up-regulates TIMP-1 expression. In the present study, we analyzed additional genes modulated by ATRA by performing mRNA expression array on alveolar macrophages after treatment with ATRA.
2010-09-04 | GSE23704 | GEO
Project description:All-trans retinoic acid (ATRA) is a potent retinoid, which has been used successfully in different clinical settings as a potential drug to treat COPD and emphysema. In alveolar macrophages, ATRA selectively down-regulates MMP-9 and up-regulates TIMP-1 expression. In the present study, we analyzed additional genes modulated by ATRA by performing mRNA expression array on alveolar macrophages after treatment with ATRA. Total RNA was isolated from BAL cells cultivated either in the presence of liposomal ATRA or left untreated for 3 days. Total RNA from five independent donors were pooled at 0.4 µg each to give a final amount of 2µg. This pooled RNA was used for microarray analysis using the Affymatrix array
2010-09-04 | E-GEOD-23704 | biostudies-arrayexpress
Project description:The main purpose of this clinical trial is to learn about the good and the bad effects of all trans retinoic acid (ATRA), atezolizumab and bevacizumab as a possible treatment for advanced colorectal patients.
Participants will be treated with the following combination of these drugs:
1. ATRA will be given in a pill form to be taken twice a day at home for 7 days starting on day 1 of a cycle.
2. Atezolizumab will be given through a vein in arm or through mediport over 60-90 minutes every 2 weeks in the outpatient chemotherapy infusion centers at UTSW.
3. Bevacizumab will be given through a vein in arm or through mediport over 20-40 minutes every 2 weeks in the outpatient chemotherapy infusion centers at UTSW.
| 70824 | ecrin-mdr-crc
Project description:Retinoids have been used as potential chemotherapeutic or chemo-preventive agents because of their differentiation, anti-proliferative, pro-apoptotic, and anti-oxidant effects. We investigated the effect of all trans- retinoic acid (ATRA) at different stages of the neoplastic transformation using an in vitro model of breast cancer progression. This model was previously developed by treating the human normal-like breast epithelial MCF-10F cells with high dose of estradiol and consist of five cell lines which shown a progressive neoplastic transformation: MCF-10F (normal stage), trMCF (premalignant stage), bsMCF (invasive stage) and caMCF (tumorigenic stage). In 3D-cultures, MCF-10F cells form tubules resembling the normal mammary gland although after treatment with high doses of estradiol, trMCF cells, formed tubules and, spherical masses which are an indication of cell transformation. By ring cloning, trMCF clone 11 which only formed spherical masses in collagen was isolated. Our results showed that the early transformed trMCF clone 11 cells shown a reduction of spherical masses and increased of tubules in collagen after being treated with 10-5M (10M-BM-5M) and 10-6M (1M-BM-5M) ATRA; the number of tubules was higher in cells treated with 10-6M ATRA (43% vs. 10% tubules). The invasive bsMCF and tumorigenic caMCF cells did not shown any changes in morphology after ATRA treatment. Analysis of expression studies in early transformed cells treated with 10-6M ATRA showed that 271 probes upregulated in trMCF clone 11 cells were downregulated after ATRA treatment and, 316 probes that were downregulated were upregulated after ATRA treatment in these cells to similar levels than the normal breast epithelial cells MCF-10F. These genes were involved in the aryl hydrocarbon receptor signaling, RAR Activation, xenobiotic metabolisms signaling, molecular mechanisms of cancer and cell morphology. Our results shown that ATRA was able to re-differentiate transformed cells at early stages of the neoplastic process suggesting that ATRA could potentially be used to inhibit the progression of premalignant lesions of the breast such as ductal carcinoma in situ (DCIS). We investigated the effect of all trans- retinoic acid (ATRA) at different stages of the neoplastic transformation using an in vitro model of breast cancer progression. This model was previously developed by treating the human normal-like breast epithelial MCF-10F cells with high dose of estradiol and consist of five cell lines which shown a progressive neoplastic transformation: MCF-10F (normal stage), trMCF (premalignant stage), bsMCF (invasive stage) and caMCF (tumorigenic stage).
2013-12-13 | E-GEOD-51549 | biostudies-arrayexpress
Project description:All-trans retinoic acid (ATRA) has been shown to have anti-proliferative effects, particularly in the context of cancer. However, the effects of ATRA on gene and microRNA expression in solid tumors have not been investigated. In this study, we performed gene expression and microRNA analysis of the squamous cell carcinoma cell line, ME180, following treatment with 10 micromolar all-trans retinoic acid (ATRA) for 1, 3, and 6 hours. Results provide insight into the temporal regulation of genes and microRNAs by retinoids.
2014-08-01 | GSE54464 | GEO
Project description:Targets of Retinoic Acid (RA) and 3,4-didehydroretinoic acid (ddRA) were identified in primary human epidermal keratinocytes grown in the presence of atRA or ddRA for 4 and 24 hours. Retinoids (natural forms and synthetic derivatives of vitamin A) are used as therapeutic agents for numerous skin diseases such as keratinization disorders (e.g. ichthyoses) and psoriasis. Two endogenous ligands for retinoic acid receptors exist, retinoic acid (atRA) and 3,4-didehydroretinoic acid (ddRA). In primary human epidermal keratinocytes many transcriptional targets for atRA are known, whereas the targets for ddRA are unknown. In an attempt to determine the targets, we compared the effect of atRA and ddRA on transcriptional profiles in undifferentiated and differentiating human primary keratinocytes. First, as expected, many genes were induced or suppressed in response to keratinocyte differentiation. Furthermore, the two retinoids affected substantially more genes in differentiated keratinocytes (more than 350) than in proliferating keratinocytes (20). In differentiating keratinocytes markers of cornification were suppressed suggesting a de-differentiating effect by the two retinoids. When comparing the expression profile of atRA to that of ddRA, no differently regulated genes were found. The array analysis also found that a minor number of miRNAs and a large number of non-coding transcripts were changed during differentiation and in response to the two retinoids. Furthermore, the expression of all, except one, genes known to cause autosomal recessive congenital ichthyosis (ARCI) were found to be induced by differentiation. These results comprehensively document that atRA and ddRA exert similar transcriptional changes in keratinocytes and also add new insights into the molecular mechanism influenced by retinoids in the epidermis. Furthermore, it suggests which ARCI patients could benefit from therapy with retinoids. Proliferating and differentiated keratinocytes were harvested after 4 and 24 hours after treatment with atRA, ddRA and vehicle for RNA extraction and hybridization on Affymetrix microarrays. Triplicate samples were generated for each time point and each treatment.
2014-08-01 | E-GEOD-58749 | biostudies-arrayexpress
Project description:Targets of Retinoic Acid (RA) and 3,4-didehydroretinoic acid (ddRA) were identified in primary human epidermal keratinocytes grown in the presence of atRA or ddRA for 4 and 24 hours. Retinoids (natural forms and synthetic derivatives of vitamin A) are used as therapeutic agents for numerous skin diseases such as keratinization disorders (e.g. ichthyoses) and psoriasis. Two endogenous ligands for retinoic acid receptors exist, retinoic acid (atRA) and 3,4-didehydroretinoic acid (ddRA). In primary human epidermal keratinocytes many transcriptional targets for atRA are known, whereas the targets for ddRA are unknown. In an attempt to determine the targets, we compared the effect of atRA and ddRA on transcriptional profiles in undifferentiated and differentiating human primary keratinocytes. First, as expected, many genes were induced or suppressed in response to keratinocyte differentiation. Furthermore, the two retinoids affected substantially more genes in differentiated keratinocytes (more than 350) than in proliferating keratinocytes (20). In differentiating keratinocytes markers of cornification were suppressed suggesting a de-differentiating effect by the two retinoids. When comparing the expression profile of atRA to that of ddRA, no differently regulated genes were found. The array analysis also found that a minor number of miRNAs and a large number of non-coding transcripts were changed during differentiation and in response to the two retinoids. Furthermore, the expression of all, except one, genes known to cause autosomal recessive congenital ichthyosis (ARCI) were found to be induced by differentiation. These results comprehensively document that atRA and ddRA exert similar transcriptional changes in keratinocytes and also add new insights into the molecular mechanism influenced by retinoids in the epidermis. Furthermore, it suggests which ARCI patients could benefit from therapy with retinoids.
2014-08-01 | GSE58749 | GEO
Project description:A role for vitamin A in host defense against Mycobacterium tuberculosis has been suggested through epidemiological and in vitro studies; however, the antimicrobial mechanism is unclear. Here, we demonstrate that vitamin A mediates host defense through regulation of cellular cholesterol content. Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3, the biologically active forms of vitamin A and vitamin D respectively, indicates that ATRA and 1,25D3 induce mechanistically distinct antimicrobial activities. Gene expression profiling reveals that ATRA but not 1,25D3 triggers a lipid metabolism and efflux pathway, including expression of lysosomal lipid transport gene NPC2. ATRA-induced decrease in total cellular cholesterol content, subcellular lipid reorganization, lysosomal acidification and antimicrobial activity are all dependent upon expression of NPC2. Finally, the addition of HIV-protease inhibitors known to inhibit cholesterol efflux, Ritonavir and Nelfinavir, blocked both ATRA-induced cholesterol decrease as well as antimicrobial activity. Taken together, these results suggest that the vitamin A-mediated host defense mechanism against M. tuberculosis requires regulation of cellular cholesterol. Monocytes derived from four independent healthy blood donors that were stimulated with control (CTRL), ATRA or 1,25D3 at 10-8M for 18 hours.
2013-12-31 | E-GEOD-46268 | biostudies-arrayexpress
Project description:A role for vitamin A in host defense against Mycobacterium tuberculosis has been suggested through epidemiological and in vitro studies; however, the antimicrobial mechanism is unclear. Here, we demonstrate that vitamin A mediates host defense through regulation of cellular cholesterol content. Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3, the biologically active forms of vitamin A and vitamin D respectively, indicates that ATRA and 1,25D3 induce mechanistically distinct antimicrobial activities. Gene expression profiling reveals that ATRA but not 1,25D3 triggers a lipid metabolism and efflux pathway, including expression of lysosomal lipid transport gene NPC2. ATRA-induced decrease in total cellular cholesterol content, subcellular lipid reorganization, lysosomal acidification and antimicrobial activity are all dependent upon expression of NPC2. Finally, the addition of HIV-protease inhibitors known to inhibit cholesterol efflux, Ritonavir and Nelfinavir, blocked both ATRA-induced cholesterol decrease as well as antimicrobial activity. Taken together, these results suggest that the vitamin A-mediated host defense mechanism against M. tuberculosis requires regulation of cellular cholesterol.
2013-12-31 | GSE46268 | GEO