Ontology highlight
ABSTRACT:
PROVIDER: PRJNA237490 | ENA |
REPOSITORIES: ENA
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Project description:Basonuclin-1 modulates epithelial plasticity and TGF-β1-induced loss of epithelial cell integrity [BNC1]
| PRJNA237493 | ENA
Project description:Basonuclin-1 modulates epithelial plasticity and TGF-β1-induced loss of epithelial cell integrity [NIAC-NTR]
| PRJNA237492 | ENA
Project description:TGF-b1-stimulation induces an epithelial dedifferentiation-process, throughout which epithelial cell sheets disintegrate and gradually switch into fibroblastic-appearing cells (EMT-like transition). Several transcription factors, some of them being TGF-b1-responsive, are functionally involved in such a switch and affect epithelial differentiation and plasticity. We used microarray-based gene expression profiling of mammary epithelial cells that actively undergo TGF-b1-induced epithelial dedifferentiation. Further, we determined gene expression changes in Basonuclin-1 knock-down cells in conjunction with TGF-b1-stimulation in order to determine a possible effect of Bnc1 on TGF-b1-responsive genes. Cells were transfected with non-silencing (control) siRNA or siRNA against Basonuclin-1 (Bnc1) for 24hrs. Subsequently, cells were treated with 5ng/ml TGF-b1 or left untreated for additional 24hrs. The experiments were performed as independent biological triplicate.
2014-03-01 | E-GEOD-54715 | biostudies-arrayexpress
Project description:TGF-b1-stimulation induces an epithelial dedifferentiation-process, throughout which epithelial cell sheets disintegrate and gradually switch into fibroblastic-appearing cells (EMT-like transition). Several transcription factors, some of them being TGF-b1-responsive, are functionally involved in such a switch and affect epithelial differentiation and plasticity. We used microarray-based gene expression profiling of mammary epithelial cells that actively undergo TGF-b1-induced epithelial dedifferentiation. Further, we determined gene expression changes in Basonuclin-1 knock-down cells in conjunction with TGF-b1-stimulation in order to determine a possible effect of Bnc1 on TGF-b1-responsive genes.
2014-03-01 | GSE54715 | GEO
Project description:We studied miRNAs and their gene targets affecting SARS-CoV-2 pathogenesis in CF airway epithelial cell models in response to TGF-β1. Small RNAseq in CF human bronchial epithelial cell line treated with TGF-β1 and miRNA profiling characterized TGF-β1 effects on the SARS-CoV-2 pathogenesis pathways. Among the effectors, we identified and validated two miRNAs targeting ACE2 mRNA using different CF and non-CF human bronchial epithelial cell models. We have shown that TGF-β1 inhibits ACE2 expression by miR-136-3p and miR-369-5p. ACE2 levels were higher in cells expressing F508del-CFTR, compared to wild-type(WT)-CFTR and TGF-β1 inhibited ACE2 in both cell types. The ACE2 protein levels were still higher in CF, compared to non-CF cells after TGF-β1 treatment. TGF-β1 prevented the functional rescue of F508del-CFTR by ETI in primary human bronchial epithelial cells while ETI did not prevent the TGF-β1 inhibition of ACE2 protein. Finally, TGF-β1 reduced binding of ACE2 to the recombinant monomeric spike RBD. Our results may help to explain, at least in part, the role of TGF-β1 on the SARS-CoV-2 entry via ACE2 in the CF and non-CF airway.
2023-04-01 | GSE226758 | GEO
Project description:Limited therapeutic responses to glucocorticoids in chronic inflammatory disease are partly attributable to interleukins and transforming growth factor-β1 (TGF-β1). Global inhibition of TGF-β1 carries known risks, including autoimmune disease. Here we elucidate the signaling pathway subserving modulation of glucocorticoid activity by TGF-β1. The proteomic response of airway epithelial cells to TGF-β1 revealed 24 candidate proteins of which 3 were prioritized by exclusion of changes induced by: TGF-β2, which lacks the modulatory activity of TGF-β1 and TGF-β3; and those of TGF-β1 that were prevented by small molecule inhibitors of non-canonical TGF-β1 signaling, that did not prevent glucocorticoid modulation. Pharmacological and genetic approaches establish that TGF-β1-induced glucocorticoid insensitivity is mediated by a novel signaling cascade involving LIM domain kinase 2 mediated phosphorylation of phospho-cofilin1 that activates phospholipase D to generate the effector(s) (lyso)phophatidic acid. This study identifies several promising drug targets that potentially enable safe modulation of TGF-β1 in chronic inflammatory diseases.
2019-01-27 | GSE104908 | GEO
Project description:An enhancer is a genomic DNA sequence that substantially enhances the transcriptional activity of a target gene by recruiting transcription factors. The large clusters of enhancers identified through the ChIP-seq analysis of histone H3 lysine 27 acetylation (H3K27ac) are called super-enhancers (SEs). This study examined the dynamics of SEs during transforming growth factor (TGF)-β1-mediated epithelial-mesenchymal transition (EMT) in the human keratinocyte cell line HaCaT. Initially, we identified the constitutive and the TGF-β1 signal-dependent SE regions across the HaCaT genome. The TGF-β1-induced SEs were detected at the loci of genes associated with the cell cycle, cell death, and extracellular matrix organization. Notably, the EMT-related mesenchymal genes such as FN1 and SERPINE1 gained the SEs on their loci in response to TGF-β1. Next, we investigated the functional role of BRD4, a transcriptional mediator that binds to the SEs, in the expression of TGF-β1-induced SE-associated genes. JQ-1, a potent inhibitor of BRD4, effectively reduced the TGF-β1-induced mRNA expression of FN1 and SERPINE1. In conclusion, this study demonstrated that the rearrangement of SEs is crucial for the transcriptional regulation of the TGF-β1-induced EMT in HaCaT cells.
2026-03-03 | GSE290958 | GEO
Project description:This study aimed to establish an epithelial-mesenchymal transition (EMT) model with an immortalized human bronchial epithelial cell line, M-BE, and to identify an EMT signature gene set. The TGF-β1-induced M-BE cells got spindle-shaped fibroblast-like morphology and lost the cell-cell contact, with down-regulated expression of epithelial marker E-cadherin and up-regulated expression of mesenchymal markers N-cadherin and Vimentin. Examined by microarray, there were 2628 genes identified as significant EMT-related, including 1490 up-regulated genes (FC > 2, fdr < 0.01) and 1138 down-regulated genes (FC < 0.5, fdr < 0.01) in TGF-β1-induced M-BE cells.
2013-10-06 | GSE40374 | GEO
Project description:Hepatic stellate cell (HSC) activation induced by transforming growth factor β (TGF-β1) plays a pivotal role in the fibrogenesis. The complex downstream mediators of TGF-β1 are largely unknown. Here, proteomics analysis and biological validation demonstrated that methionine adenosyltransferase 2A (MAT2A) was significantly upregulated in a CCl4-induced fibrosis mice model and a small molecule NPLC0393, known to block TGF-β1/Smad3 signaling, inhibited its upregulation. In HSC cells, TGF-β1 induced elevation of MAT2A and MAT2β expression as well as reduction of S-adenosylmethionine (SAM) content, which further promoted HSC activation. Functionally, in vivo and in vitro knockdown of MAT2A alleviated CCl4- and TGF-β1-induced HSC activation, whereas in vivo overexpression of MAT2A facilitated hepatic fibrosis and abolished therapeutic effect of NPLC0393. TGF-β1 induced p65 phosphorylation and NF-κB activation, thereby promoted the transcription of MAT2A and its protein expression. In addition, overexpression of p65 abrogated NPLC0393 mediated inhibition of HSC activation. This study identified a novel pathway TGF-β1/p65/MAT2A that was involved in the regulation of intracellular SAM contents and liver fibrogenesis, suggesting that this pathway is a potential therapeutic target for hepatic fibrosis.
2019-11-12 | PXD011134 | Pride
Project description:Hepatic stellate cell (HSC) activation induced by transforming growth factor β (TGF-β1) plays a pivotal role in the fibrogenesis. The complex downstream mediators of TGF-β1 are largely unknown. Here, proteomics analysis and biological validation demonstrated that methionine adenosyltransferase 2A (MAT2A) was significantly upregulated in a CCl4-induced fibrosis mice model and a small molecule NPLC0393, known to block TGF-β1/Smad3 signaling, inhibited its upregulation. In HSC cells, TGF-β1 induced elevation of MAT2A and MAT2β expression as well as reduction of S-adenosylmethionine (SAM) content, which further promoted HSC activation. Functionally, in vivo and in vitro knockdown of MAT2A alleviated CCl4- and TGF-β1-induced HSC activation, whereas in vivo overexpression of MAT2A facilitated hepatic fibrosis and abolished therapeutic effect of NPLC0393. TGF-β1 induced p65 phosphorylation and NF-κB activation, thereby promoted the transcription of MAT2A and its protein expression. In addition, overexpression of p65 abrogated NPLC0393 mediated inhibition of HSC activation. This study identified a novel pathway TGF-β1/p65/MAT2A that was involved in the regulation of intracellular SAM contents and liver fibrogenesis, suggesting that this pathway is a potential therapeutic target for hepatic fibrosis.
2019-11-12 | PXD011135 | Pride