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Blockage of retinoic acid signaling via RARγ suppressed the proliferation of pancreatic cancer cells by arresting the cell cycle progression of the G1-S phase

ABSTRACT: Blockage of RARγ signaling broadly downregulated the gene expression associated with the cell cycle progression of the G1-S phase and DNA synthesis in PDAC cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE210112 | GEO | 2023/08/08

REPOSITORIES: GEO

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Discovery of Dihydropyrrol-2-ones as Novel G0/G1-Phase Arresting Agents Inducing Apoptosis.

Project description: Not available

| S-EPMC6812110 | biostudies-literature

Non-clinical and clinical pharmacology of the potent and selective RARγ agonist trifarotene

Project description:Background: First- and third-generation retinoids are the main treatment in acne. Even though efficacious, they lack full selectivity for RARγ expressed in the epidermis and infundibulum. Objectives: To characterize the in vitro metabolism and the pharmacology of the novel retinoid trifarotene. Methods: In vitro assays determined efficacy, potency and selectivity on RARs, as well as the activity on the expression of retinoid target genes in human keratinocytes and ex vivo cultured skin. In vivo studies investigated topical comedolytic, anti-inflammatory and depigmenting properties. The trifarotene-induced gene expression profile was investigated in non-lesional skin of acne patients and compared to ex vivo and in vivo models. Finally, the metabolic stability in human keratinocytes and hepatic microsomes was established. Results: Trifarotene is a selective RARγ agonist with >20-fold selectivity over RAR and RARβ. Trifarotene is active and stable in keratinocytes but rapidly metabolized by human hepatic microsomes, predicting improved safety. In vivo, trifarotene 0.01% applied topically is highly comedolytic and has antiinflammatory and antipigmenting properties. Gene expression studies indicated potent activation of known retinoid-modulated processes (epidermal differentiation, proliferation, stress response, RA metabolism) and novel pathways (proteolysis, transport/skin hydration, cell adhesion) in ex vivo and in vivo models, as well as in human skin after four weeks of topical application of trifarotene 0.005% cream. Conclusion: Based on its RARγ selectivity, rapid degradation in human hepatic microsomes and pharmacological properties including potent modulation of epidermal processes, topical treatment with trifarotene is expected to provide strong efficacy combined with a favourable safety profile in acne and ichthyotic disorders.

2018-04-28 | GSE107232 | GEO

Transcription profiling of mouse normal tail skin (no intervention), lymphedema tail skin(due to surgical lymphatic vessel blockage), and surgical Sham control tail skin(surgical incision with no lymphatic vessel blockage)

Project description:We did three sets of microarrays with three replicates each for a total of 9 arrays. Each array was run using pooled RNA from three animals. The three conditions were Normal tail skin (no intervention), Lymphedema tail skin(due to surgical lymphatic vessel blockage), and Surgical Sham control tail skin(surgical incision with no lymphatic vessel blockage). 15ug of test and reference (e17.5 mouse whole embryo) RNA was used for labeling.

2006-06-06 | E-SMDB-3634 | biostudies-arrayexpress

CD22 blockage restores age-related impairments of microglia surveillance capacity

Project description:We report that antibody-mediated CD22 blockage leads to an altered transcriptomic signature profile which, by further evaluating the affected genes, resembles a homeostatic phenotype.

2021-03-30 | GSE169252 | GEO

Synthesis and Anti-Hepatoma Activities of U12 Derivatives Arresting G0/G1 Phase and Inducing Apoptosis by PI3K/AKT/mTOR Pathway.

Project description: Not available

| S-EPMC8781819 | biostudies-literature

RARγ is required for mesodermal gene expression prior to gastrulation

Project description:RARγ is required for mesodermal gene expression prior to gastrulation

| PRJNA488225 | ENA

RARγ is required for mesodermal gene expression prior to gastrulation

Project description:The developing vertebrate embryo is exquisitely sensitive to retinoic acid (RA) concentration, particularly during anteroposterior patterning. In contrast to Nodal and Wnt signaling, RA was not previously considered to be an instructive signal in mesoderm formation during gastrulation. Here we show that RARγ is indispensable for the expression of early mesoderm markers and is, therefore, an obligatory factor in mesodermal competence and/or maintenance. We identified several novel targets up-regulated by RAR signaling in the early gastrula that are expressed in the circumblastoporal ring and linked to mesodermal development. Despite overlapping expression patterns of the RA synthetic enzyme, Aldh1a2 and the RA- degrading enzyme, Cyp26a1, RARγ1 functions as a transcriptional activator in early mesoderm development, suggesting that RA ligand is available to the embryo earlier than previously appreciated. RARγ1 is required for cellular adhesion, as revealed by spontaneous dissociation and depletion of N-CAM mRNA in animal caps harvested from RARγ1 knockdown embryos. RARγ1 knockdown obliterates somite boundaries, and causes loss of MYOD protein in the presomitic mesoderm, but ectopic, persistent expression of MYOD protein in the trunk. Thus, RARγ1 is required for stabilizing the mesodermal fate, myogenic commitment, somite boundary formation, and terminal, skeletal muscle differentiation.

2018-08-29 | GSE119124 | GEO

Transcript levels in CCE WT and RARgamma knockout murine embryonic stem cells treated with either all-trans retinoic acid (8 and 24 hr) or with vehicle control

Project description:Retinoic acid receptors (RARs) α, β, and γ heterodimerize with Retinoid X receptors (RXR) α, β, and γ and bind the cis-acting response elements known as RAREs to execute the biological functions of retinoic acid during mammalian development. RARγ mediates the anti-proliferative and apoptotic effects of retinoids in certain tissues and cancer cells, such as melanoma and neuroblastoma cells. Furthermore, ablation of RARγ enhanced the tumor incidence of Ras transformed keratinocytes and was associated with resistance to retinoid mediated growth arrest and apoptosis. We used microarray analysis to identify genes, which upon 8 or 24 hr of treatment with all-trans retinoic acid display differential expression in RARγ knockout (RARγKO) murine embryonic stem cells relative to CCE WT cells. We demonstrate that following RA treatment the majority of inducible transcripts are present at lower levels in RARγKO ES cells compared to WT ES cells.

2012-12-31 | GSE43221 | GEO

CD22 blockage restores age-related impairments of microglia surveillance capacity

Project description:CD22 blockage restores age-related impairments of microglia surveillance capacity

| PRJNA715777 | ENA

Temporal activation of NR5A2 and RARγ induce functional human naïve pluripotent state via modulating TGFβ pathway

Project description:Rejuvenated primed human pluripotent stem cells, naïve cells, are accessible through the manipulating transcription factors, singaling pathways or a combination of both. However, there is a notable challenge in the functions of naïve hPSCs. Here, we show that the brief treatment with two chemical agonists (2a) of nuclear receptors NR5A2 and RARγ along with 2i and lif (2a2iL) is sufficient to induce naive pluripotency during the reprogramming of fibroblasts and pre-established hPSCs as well as the generation of new cell lines from preimplantation embryos. These cells manifested global naive-specific critera especially the contribution into the human-mouse chimeras. We demonstrated that TGF-β pathway activity is potentially critical for induction and maintenance of 2a2iL naive hPSCs. Consequently, transient activation of TGF-β resulted in generation of naive hPSCs in 2iL condition. These results represent a naive pluripotent state which is in a top point of developmental potential equivalent with preimplantation human embryo.

2018-07-03 | GSE116501 | GEO

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