Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA200284 | ENA |
REPOSITORIES: ENA
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Project description:Transforming growth factor (TGF)-β plays crucial roles in embryonic development and adult tissue homeostasis by eliciting various cellular responses in target cells. TGF-β signaling is principally mediated through receptor-activated Smad proteins, which regulate expression of target genes in cooperation with other DNA-binding transcriptionfactors (Smad cofactors). In this study, we found that the basic helix-loop-helix transcription factor Olig1 is a Smad cofactor involved in TGF-b-induced cell motility. Knockdown of Olig1 attenuated TGF-β-induced cell motility in chamber migration and wound healing assays. In contrast, Olig1 knockdown had no effect on bone morphogenetic protein-induced cell motility, TGF-β-induced cytostasis or epithelial-mesenchymal transition. Furthermore, we observed that cooperation of Smad2/3 with Olig1 is regulated by a peptidyl-prolyl cis/trans isomerase, Pin1. TGF-b-induced cell motility, induction of Olig1-regulated genes, and physical interaction between Smad2/3 and Olig1 were all inhibited after knockdown of Pin1, indicating a novel mode of regulation of Smad signaling. We also found that Olig1 interacts with the L3 loop of Smad3. Using a synthetic peptide corresponding to the L3 loop of Smad3, we succeeded in selectively inhibiting TGF-b-induced cell motility. These findings may lead to a new strategy for selective regulation of TGF-b-induced cellular responses. NMuMG cells were transfected with siRNAs (siControl, siOlig1 or siPin1) and treated with or without TGF-b for 1h. We compared genes affected by knockdown of Olig1 and that of Pin1.
2013-07-01 | E-GEOD-46405 | biostudies-arrayexpress
Project description:Transforming growth factor (TGF)-β plays crucial roles in embryonic development and adult tissue homeostasis by eliciting various cellular responses in target cells. TGF-β signaling is principally mediated through receptor-activated Smad proteins, which regulate expression of target genes in cooperation with other DNA-binding transcriptionfactors (Smad cofactors). In this study, we found that the basic helix-loop-helix transcription factor Olig1 is a Smad cofactor involved in TGF-b-induced cell motility. Knockdown of Olig1 attenuated TGF-β-induced cell motility in chamber migration and wound healing assays. In contrast, Olig1 knockdown had no effect on bone morphogenetic protein-induced cell motility, TGF-β-induced cytostasis or epithelial-mesenchymal transition. Furthermore, we observed that cooperation of Smad2/3 with Olig1 is regulated by a peptidyl-prolyl cis/trans isomerase, Pin1. TGF-b-induced cell motility, induction of Olig1-regulated genes, and physical interaction between Smad2/3 and Olig1 were all inhibited after knockdown of Pin1, indicating a novel mode of regulation of Smad signaling. We also found that Olig1 interacts with the L3 loop of Smad3. Using a synthetic peptide corresponding to the L3 loop of Smad3, we succeeded in selectively inhibiting TGF-b-induced cell motility. These findings may lead to a new strategy for selective regulation of TGF-b-induced cellular responses.
2013-07-01 | GSE46405 | GEO
Project description:Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3-TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins MyD88 and Toll interleukin receptor 1 domain-containing adapter-inducing interferon beta, which together mediate all TLR MyD88-dependent and -independent NF-kappaB signaling, did not phosphorylate NF-kappaB p65 or Smad-induced IkappaBalpha, and did not translocate NF-kappaB into the nucleus. Importantly, transforming growth factor-beta released from intestinal extracellular matrix (stroma) induced identical down-regulation in the NF-kappaB signaling and function of blood monocytes, the exclusive source of intestinal macrophages. Our findings implicate stromal transforming growth factor-beta-induced dysregulation of NF-kappaB proteins and Smad signaling in the differentiation of pro-inflammatory blood monocytes into noninflammatory intestinal macrophages. Comparison of unstimulated monocytes and macrophages, and flagellin stimulated monocytes and macrophages.
2010-07-07 | E-GEOD-22373 | biostudies-arrayexpress
Project description:Transcriptome profiling of Transforming Growth Factor B1-Induced Mesangial Gene Expression
| PRJNA92171 | ENA
Project description:Transforming growth factor- (TGF-) signaling is a critical driver of epithelial–mesenchymal transition (EMT) and cancer progression. However, the regulatory roles of long non-coding RNAs (lncRNAs) in TGF--induced EMT and cancer progression are not well understood. Here, we identified an unannotated nuclear lncRNA LETS1 (LncRNA Enforcing TGF- Signaling 1) as a novel TGF-/SMAD target gene. Loss of LETS1 attenuates TGF--induced EMT, migration and extravasation in breast and lung cancer cells. LETS1 potentiates TGF-/SMAD signaling by stabilizing cell surface TGF- type I receptor (TRI) and thereby forms a positive feedback loop. Mechanistically, LETS1 inhibits TRI polyubiquitination by inducing the orphan nuclear receptor 4A1 (NR4A1) expression, a critical determinant of a destruction complex for inhibitory SMAD7. An unbiased interactome analysis identified the Nuclear Factor of Activated T Cells (NFAT5) as a protein partner of LETS1 to mediate activation of NR4A1 promoter. Overall, our findings characterize LETS1 as an EMT-promoting lncRNA and elucidate the mechanism by which nuclear LETS1 potentiates TGF- receptor signaling.
2023-07-31 | PXD037401 | Pride
Project description:Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3-TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins MyD88 and Toll interleukin receptor 1 domain-containing adapter-inducing interferon beta, which together mediate all TLR MyD88-dependent and -independent NF-kappaB signaling, did not phosphorylate NF-kappaB p65 or Smad-induced IkappaBalpha, and did not translocate NF-kappaB into the nucleus. Importantly, transforming growth factor-beta released from intestinal extracellular matrix (stroma) induced identical down-regulation in the NF-kappaB signaling and function of blood monocytes, the exclusive source of intestinal macrophages. Our findings implicate stromal transforming growth factor-beta-induced dysregulation of NF-kappaB proteins and Smad signaling in the differentiation of pro-inflammatory blood monocytes into noninflammatory intestinal macrophages.
2010-06-22 | GSE22373 | GEO
Project description:Transforming growth factor-β (TGFβ) is a potent inhibitor of hematopoietic stem cell (HSC) proliferation. However, the precise mechanism for this effect is unknown. Here, we have identified the transcription factor Gata2, previously described as an important regulator of HSC function, as an early and direct target gene for TGFβ-induced Smad signaling in hematopoietic stem and progenitor cells (HSPCs). Interestingly, TGFβ-induced Gata2 upregulation is critical for subsequent transcriptional activation of the TGFβ signaling effector molecule p57 and resulting growth arrest of HSPCs. Importantly, both Gata2 and p57 are abundantly expressed in freshly isolated highly purified HSCs, demonstrating the relevance of this circuit in HSC regulation within the HSC niche. Our results connect key molecules involved in HSC self-renewal and reveal a functionally relevant network regulating proliferation of primitive hematopoietic cells. To identify TGFβ targets downstream of Gata2, we carried out a ChIP-Seq experiment on TGFβ-induced Lhx2 cells. Interestingly, there was a large overlap between the GATA2-bound genes and genes differentially expressed after 2h TGFβ induction. One sample of 1x10^8 cells (treated with 10 ng/ml TGFβ for 2h) was sequenced.
2016-09-01 | E-GEOD-73641 | biostudies-arrayexpress
Project description:Schisandra chinensis fruit extract (SCE) and its active ingredient Schisandrin B (SchB), which are effective in the treatment of vascular diseases, have been known to suppress transforming growth factor β1 (TGF-β1)-mediated Smad activation and myosin light chain (MLC) phosphorylation in vascular smooth muscle cells (VSMCs). However, it is still largely unknown about the pharmacologic effects and mechanisms of SCE and SchB on TGF-β1-induced intracellular signaling pathways in vascular smooth muscle cells (VSMCs).
2017-12-20 | GSE87439 | GEO
Project description:Spleen vs TGF-beta (transforming growth factor-beta) Treated B cell
| PRJNA84941 | ENA
Project description:Myelination by oligodendrocytes in the central nervous system (CNS) is essential for proper brain function, yet the molecular determinants that control this process remain poorly understood. The basic helix-loop-helix transcription factors Olig1 and Olig2 promote myelination, whereas bone morphogenetic protein (BMP) and Wnt/β-catenin signaling inhibit myelination. Here we show that these opposing regulators of myelination are functionally linked by the Olig1/2 common target Smad-interacting protein-1 (Sip1). We demonstrate that Sip1 is an essential modulator of CNS myelination. Sip1 represses differentiation inhibitory signals by antagonizing BMP receptor-activated Smad activity while activating crucial oligodendrocyte-promoting factors. Importantly, a key Sip1-activated target, Smad7, is required for oligodendrocyte differentiation and partially rescues differentiation defects caused by Sip1 loss. Smad7 promotes myelination by blocking the BMP- and β-catenin-negative regulatory pathways. Thus, our findings reveal that Sip1-mediated antagonism of inhibitory signaling is critical for promoting CNS myelination and point to new mediators for myelin repair. We carried out microarray profiling analysis in the Sip1 conditional KO (cKO) mouse spinal cord to detail the change of global gene expression. Sip1 c/c;Olig1-Cre mouse spinal cord was collected at P14 for RNA extraction and Affymetrix microarray analysis. Sip1 c/+;Olig1-Cre littermate spinal cord was used as the control.
2012-08-31 | E-GEOD-40510 | biostudies-arrayexpress