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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: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: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
Project description:Vicious circle of some key proteins is critical in the process of tumor development. Nevertheless, the mechanism of how the epigenetic modifiers are involved in was seldom reported and has not been clearly illustrated. We found the expression of lysine specific demethylase 1 (LSD1), the first identified histone lysine demethylase, is positively correlated with transforming growth factor beta 1 (TGF β1) in gastric cancer tissues and can be promoted by TGF β1 activated (p-EKR)-(NF-κB)-p300 signaling pathway, which resulted in the progression of epithelial-mesenchymal transition (EMT) in human gastric cancer cells. On the other hand, abrogation of LSD1 leads to the down regulation of TGF β1 as well as the EMT. But in benign cells, this circle was blocked by TGF β1 induced inactivation of ERK, which suggested the distinct roles of TGF β1 against LSD1 in gastric cancer cells and benign cells. This vicious cycle may illustrate a novel mechanism for EMT in gastric cancer mediate by TGF β1 and LSD1 but not in benign cells and may serve as a new strategy for the prevention of EMT for gastric cancer.
2016-07-19 | GSE84487 | GEO
Project description:Fibrotic diseases have significant health impact and have been associated with differentiation of the resident fibroblasts into myofibroblasts. In particular, stiffened extracellular matrix and TGF-β1 in fibrotic lesions have been shown to promote pathogenic myofibroblast activation and progression of fibrosis in various tissues. To better understand the roles of mechanical and chemical cues on myofibroblast differentiation and how they may crosstalk, we cultured primary valvular interstitial cells (VICs) isolated from porcine aortic valves and studied how traditional TCPS culture, which presents a non-physiologically stiff environment, and TGF-β1 affect native VIC phenotypes. We carried out gene expression profiling using porcine genome microarrays from Affymetrix and found that traditional TCPS culture induces major changes in gene expression of native VICs, rendering these cells more activated and similar to cells treated with TGF-β1. We also monitored time-dependent effects induced by TGF-β1 by examining gene expression changes induced by TGF-β1 at 8 hours and 24 hours. Porcine aortic VICs were isolated and cultured with or without TGF-β1 treatment for RNA extraction and hybridization on Affymetrix microarrays. We included 3 biological replicates for each condition. P0 VICs were freshly isolated cells which had not been cultured. P2 VICs were cells that had been passaged 2 times and cultured on plastic plates in low serum media. Some of the P2 VICs were treated with TGF-β1 at 5ng/ml for 8 hours or 24 hours. All the control and TGF-β1-treated conditions were collected at the same time on day 3 of culture.
2013-09-02 | E-GEOD-48839 | biostudies-arrayexpress
Project description:To identify differentially expressed long noncoding RNAs (lncRNAs) upon TGF-β stimulation in human cultured tubular epithelial cells HK2 and HKC8, we have employed long noncoding RNA microarray expression profiling as a discovery platform to find differentially expressed lncRNAs with TGF-β stimulation in these cells. Cultured human tubular epithelial cells HK2 and HKC8 were stimulated with PBS or TGF-β1. After incubation with TGF-β1 (10ng/ml) for 24 hours, 86 overlapping lncRNAs were upregulated and 47 overlapping lncRNAs were downregulated more than 2 fold vesus cells treated with PBS in these two epithelial cell lines. Expression of ENST00000429588 from this result was quantified in the same RNA samples by real-time PCR, confirming the upregulation upon TGF-β stimulation is repeatable.
2018-08-15 | GSE108554 | GEO