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Project description:Conjunctival goblet cell loss in ocular surface diseases is accompanied by increased number of interleukin-12 (IL-12)-producing antigen-presenting cells (APCs) and increased interferon-? (IFN-?) expression. This study tested the hypothesis that mouse conjunctival goblet cells produce biologically active retinoic acid (RA) that suppresses CD86 expression and IL-12 production by myeloid cells. We found that conditioned media from cultured conjunctival goblet cells (CjCM) suppressed stimulated CD86 expression, NF-?B p65 activation and IL-12 and IFN-? production in unstimulated and lipopolysaccharide-stimulated cultured bone marrow-derived cells (BMDCs) containing a mixed population of APCs. Goblet cell-conditioned, ovalbumin-loaded APCs suppressed IFN-? production and increased IL-13 production in co-cultured OTII cells. The goblet cell suppressive activity is due in part to their ability to synthesize RA from retinol. Conjunctival goblet cells had greater expression of aldehyde dehydrogenases Aldh1a1 and a3 and ALDEFLUOR activity than cornea epithelium lacking goblet cells. The conditioning activity was lost in goblet cells treated with an ALDH inhibitor, and a retinoid receptor alpha antagonist blocked the suppressive effects of CjCM on IL-12 production. Similar to RA, CjCM increased expression of suppressor of cytokine signaling 3 (SOCS3) in BMDCs. SOCS3 silencing reversed the IL-12-suppressive effects of CjCM. Our findings indicate that conjunctival goblet cells are capable of synthesizing RA from retinol secreted by the lacrimal gland into tears that can condition APCs. Evidence suggests goblet cell RA may function in maintaining conjunctival immune tolerance and loss of conjunctival goblet cells may contribute to increased Th1 priming in dry eye.
| S-EPMC6153729 | biostudies-literature
Project description:Recent studies demonstrated that stromal cells isolated from adult bone marrow have the competence of differentiating into neuronal cells in vitro and in vivo. However, the capacity of marrow stromal cells or mesenchymal stem cells (MSCs) to differentiate into diverse neuronal cell populations and the identity of molecular factors that confer marrow stromal cells with the competence of a neuronal subtype have yet to be elucidated. Here, we show that Sonic hedgehog (Shh) and retinoic acid (RA), signaling molecules secreted from tissues in the vicinity of peripheral sensory ganglia during embryogenesis, exert synergistic effects on neural-competent MSCs to express a comprehensive set of glutamatergic sensory neuron markers. Application of Shh or RA alone had little or no effect on the expression of these neuronal subtype markers. In addition, incubation of MSCs with embryonic hindbrain/somite/otocyst conditioned medium or prenatal cochlea explants promoted up-regulation of additional sensory neuron markers and process outgrowth. These results identify Shh and RA as sensory competence factors for adult pluripotent cells and establish the importance of interactions between adult pluripotent cells and the host microenvironment in neuronal subtype specification.
| S-EPMC555703 | biostudies-literature
Project description:Bone marrow-derived mesenchymal stem cells are multipotent stem cells, an attractive resource for regenerative medicine. Accumulating evidence suggests that all-trans retinoic acid plays a key role in the development and differentiation of smooth muscle cells. In the present study, we demonstrate, for the first time, that rabbit bone marrow-derived mesenchymal stem cells differentiate into smooth muscle cells upon the treatment with all-trans retinoic acid. All-trans retinoic acid increased the expression of myocardin, caldesmon, 22-kDa smooth muscle cell-specific protein (SM22alpha), and SM-myosin heavy chains in rabbit bone marrow-derived mesenchymal stem cells, as detected by reverse transcription polymerase chain reaction (PCR). Immunostaining of SM22alpha and SM-myosin heavy chains using monoclonal antibodies also indicated smooth muscle cell differentiation of rabbit bone marrow-derived mesenchymal stem cells following the treatment with all-trans retinoic acid. In addition, more than 47% of bone marrow-derived mesenchymal stem cells demonstrated the contractile phenotype of smooth muscle cells. Western blot results showed that SM-1 and SM-2 were highly expressed in the differentiated cells. These results suggest that all-trans retinoic acid may serve as a potent agent for functional smooth muscle cell differentiation in tissue engineering.
| S-EPMC2897018 | biostudies-literature
Project description:We are presenting the application of toxicogenomics in the evaluation of the toxic effects of retinoic acid and one of its isoforms the 9-cis retinoic acid. The main goal is to distinguish the pattern of action of the both chemical compounds and their action in an extended exposure. The results suggest a different pattern within the days and the chemicals. Representatives of each GO functional groups were selected and quantified by real-time PCR to validate the microarray data and to differentiate the action of retinoic acid compounds studied.
2015-12-31 | GSE41335 | GEO
Project description:We aimed to investigate the E-box and Max-independent functions of the oncogene Myc in gene regulation and differentiation of leukemic cells. Expression in HL60 leukemic cells of a mutant form of Myc with impaired Max and E-box interaction by replacing the phosphorylation sites of Pak2 kinase to aspartic acid (MycD), resulted in downregulation of 235 genes and, interestingly, upregulation of 586 genes. Eleven percent of the genes upregulated by MycD coincided with those stimulated by a short treatment of retinoic acid (RA) alone. When leukemic cells expressing MycD were stimulated with RA, the overlap with the RA-alone signature increased to 32% (492/1556 genes). Importantly, 320 of these 492 bona-fide direct RA target genes were specifically superactivated in presence of MycD (MycD+RA>RA), and not by MycA (MycD+RA>MycA+RA), further suggesting a synergy between the two pathways. The list of superactivated genes included important regulators of development and differentiation such as GATA6, ICAM1 and HOX genes, whose expression was validated in independent experiments by RT-qPCR. Induced gene expression in HL60 cells was measured after a short-treatment of retinoic acid (100nM, 4 hours). Cells were either wild-type or expressing ER-tagged MycD or MycA. Four biologically independent experiments were performed at each time.
2012-01-05 | E-GEOD-24731 | biostudies-arrayexpress
Project description:Retinoic acid promotes the in vitro growth, patterning and improves the cellular composition of human pluripotent stem-cell-derived intestinal organoids
2022-09-02 | GSE212333 | GEO
Project description:Comparison of gene expressions among osteogenic differentiated cells with retinoic acid, those without retinoic acid and cells before induction
2018-12-21 | GSE119577 | GEO
Project description:We performed pulldown assays followed by mass-spectrometry analysis using biotin-tagged 13-cis retinoic acid to identify its binding targets in HeLa cells
2022-01-14 | PXD029579 | Pride
Project description:Neural induction of ES by Retinoic acid Neural induction of ES by Retinoic acid
2010-06-11 | E-GEOD-4075 | biostudies-arrayexpress
Project description:It is unknown how dendritic cells (DCs) become specialized as mucosal DCs and maintain intestinal homeostasis. We report that a subset of bone marrow cells freshly isolated from C57BL/6 mice express the retinoic acid (RA)-synthesizing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1a2) and are capable of providing RA to DC precursors in the bone marrow microenvironment. RA induced bone marrow-derived DCs to express CCR9 and ALDH1a2 and conferred upon them mucosal DC functions, including induction of Foxp3(+) regulatory T cells, IgA-secreting B cells, and gut-homing molecules. This response of DCs to RA was dependent on a narrow time window and stringent dose effect. RA promoted bone marrow-derived DC production of bioactive TGF-? by inhibiting suppressor of cytokine signaling 3 expression and thereby enhancing STAT3 activation. These RA effects were evident in vivo, in that mucosal DCs from vitamin A-deficient mice had reduced mucosal DC function, namely failure to induce Foxp3(+) regulatory T cells. Furthermore, MyD88 signaling enhanced RA-educated DC ALDH1a2 expression and was required for optimal TGF-? production. These data indicate that RA plays a critical role in the generation of mucosal DCs from bone marrow and in their functional activity.
| S-EPMC4454342 | biostudies-literature