Inflammation drives TGFβ1 activation via the αvβ6 integrin-mechanotransduction pathway in human skin
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE298207 | GEO | 2025/05/28
REPOSITORIES: GEO
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Project description:Inflammation drives TGFβ1 activation via the αvβ6 integrin-mechanotransduction pathway in human skin
| PRJNA1268517 | ENA
Project description:To investigate TGFβ1 (a key member of the TGFβ superfamily) signaling in non-cancerous and cancerous cells derived from breast epithelium and what further response it might generate, we treated the cells with TGFβ1 or with conditioned media. We selected MCF10A non-tumorigenic breast epithelial cells (isolated from the mammary gland with fibrocystic disease) and MCF7 breast adenocarcinoma cells (estrogen receptor-positive, ER+). We followed a regimen of treating the cells for six consecutive days, with daily administration of TGFβ1 for two hours. The TGFβ1-containing medium was changed to a fresh one, which was collected after another 22 hours (so-called conditioned medium, CM) and administered to other cells. This enabled us to assess the ability of extracellularly secreted molecules to further induce a cellular response (bystander effect). RNA-seq analyses were performed on cells either directly treated with TGFβ1 in the above scheme or treated with a conditioned media for 1, 2, 3, 4, 5, or 6 days. The experiment was performed in three biological replicates, and each sample was sequenced separately. RNA-seg analysis in both cell lines allowed us to find the differences and similarities in response to TGFβ1 and CM. All 84 libraries were sequenced on Illumina NovaSeq6000 platform, in 2x150 mode, with a coverage of 60M reads/sample.
2024-12-01 | E-MTAB-13865 | biostudies-arrayexpress
Project description:Fibrosis is an uncontrolled wound healing process resulting from tissue injury, inflammation and fibroblast activation, finally leading to accumulation of extracellular matrix (ECM) components in tissues and to organ failure. The underlying mechanisms of fibrosis have been intensely studied and it has become clear that multiple pathways and their crosstalk regulate fibrotic diseases with a few central players, including TGFβ1. Recently, YAP and TAZ were implicated in fibrosis as one of the essential components of its pathogenesis. YAP/TAZ are known to crosstalk with the TGFβ pathway in the nucleus and regulate its activity on transcriptional level by binding to Smad2/3/4 complexes. We hypothesized that factors, such as GPCR ligands which regulate YAP/TAZ, might modulate the profibrotic responses to TGFβ1. We performed gene expression microarray in NHDF treated with TGFβ1, LPA, the combination of TGFβ1/LPA or vehicle. The aim was to have a broader look at transcriptional signatures induced by the individual treatments and in the combination of TGFβ1 and LPA.
2020-01-27 | GSE125519 | GEO
Project description:Mechanical cues play a vital role in numerous biological processes, including embryonic development, aging, cellular homeostasis, and disease progression. Cells sense and convert these mechanical signals into biochemical responses that regulate cell behaviours like proliferation and migration through a process known as mechanotransduction. In this study, we present a comprehensive, large-scale approach to identify proteins with a mechanosensitive nuclear localisation and therefore a potential role in mechanotransduction. Our screening method is based on inducing acute changes in cellular traction forces, combined with in situ biotinylation of nuclear proteins, followed by mass spectrometry analysis. This screen approach identified among other proteins the splicing factor PTBP1 as a protein with mechanosensitive nuclear localisation, and we show that its nuclear abundance can be regulated by mechanical cues such as cell density, cell size, and extracellular matrix (ECM) stiffness. Moreover, we demonstrate that PTBP1 is essential for ECM stiffness-driven mesenchymal stem cell differentiation into osteoblasts, as well as for epithelial cell spreading and stiffness-induced proliferation. Furthermore, we show that PTBP1 mediates mechanosensitive alternative splicing of the endocytic adapter protein Numb, and that this splicing event affects the membrane trafficking of the mechanosensor integrin beta1 and is critical for matrix stiffness-induced stem cell differentiation and epithelial cell proliferation and cell spreading. Our findings support the emerging concept that alternative splicing plays a crucial role in mechanotransduction, offering new mechanistic insights into how matrix stiffness influences cellular mechanoresponses.
2025-03-30 | GSE279391 | GEO
Project description:Mechanical force is a fundamental regulator of bone development and homeostasis. Mechanosensitive osteocytes are the most abundant bone cells that form interconnected dendrites to respond to mechanical stimuli and interact with the bone-forming osteoblasts and the bone-remodeling osteoclasts. However, the molecular mechanisms underlying osteocyte maturation and dendrite formation remain unclear. By generating a Piezo1 "knock-out" osteocyte cell line, we identified a key role of Piezo1-mediated mechanotransduction in osteocyte differentiation. QRT-PCR analysis revealed delayed osteocyte differentiation in the Piezo1 KO cells relative to WT cells. By performing bulk RNA sequencing of WT and Piezo1 KO OCY454 cells at early (D1), intermediate (D14), and late (D28) stages of differentiation allowed for the identification of key signaling pathways in driving normal osteocyte dfiferentiation, as well as those regulated by Piezo1 mechanotransduction.
2024-09-20 | GSE277264 | GEO
Project description:Deep review of our previous model MODEL2302150001 and publication Dent et al., 2015 (Mechanotransduction map: simulation model, molecular pathway, gene set) with more mechanical stimuli and specific attention to the impact on inflammation and on the AhR receptor.
2025-04-03 | MODEL2406110001 | BioModels
Project description:4 replicates were prepared from A2058 melanoma cells [transfected with 10ng of empty vector (pcDNA3.1+)] and treated with 5ng/ml TGFβ1 or vehicle control for 24hrs This is the control arm of a larger experiment where cells transfected with a particular expression plasmid were treated with TGFβ1 or control vehicle. The transfection with the expresion plasmid was unsucessful so this empty vector data has been used alone to simply examine the effect of TGFβ1 treatment on A2058 cells.
2015-02-20 | E-GEOD-66114 | biostudies-arrayexpress
Project description:TGFβ is known to be a potent inducer of EMT, a process involved in tumor invasion. TIF1γ has been reported to participate to TGFβ signaling. In order to understand the role of TIF1γ in TGFβ signaling and its requirement for EMT, we analyzed the TGFβ1 response of human mammary epithelial cell lines. A strong EMT increase was observed in TIF1γ-silenced cells after TGFβ1 treatment, whereas Smad4 inactivation completely blocked this process. In support of these observations, microarray data show that the functions of several TIF1γ target genes can be linked to EMT. As a negative regulator of Smad4, TIF1γ could be critical for the regulation of TGFβ signaling. This work highlights the molecular relationship between TIF1γ and Smad4 in TGFβ1 signaling and EMT. Total mRNA extractions were performed for 11 samples from transfected HMEC-TR. Replicates are rimo1, 6; rimo3, 9; rimo2, 7; rimo 4, 10 and rimo 5, 11. Rimo 8 is a single experiment. All RNA extractions were obtained from two independent cell cultures excepted for rimo8. Rimo 1, 6 are replicate for ctrl-; Rimo 3, 9 are replicate for ctrl+; Rimo 2, 7 are replicate for SiTIF-; Rimo 4, 10 are replicate for SiTIF+; Rimo8 is SiSmad4-; and Rimo5, 11 are replicate for SiSmad4+. ctrl means that HMEC-TR were transfected with an SiRNA scramble. "siSmad4" means that HMEC-TR were transfected with an SiRNA anti Smad4. "siTIF" means that HMEC-TR were transfected with an SiRNA anti TIF1γ. "-" means that cells were grown without TGFβ. "+" means that cells were treated with 5 ng/ml TGFβ1 for 24h.
2011-05-26 | E-GEOD-28448 | biostudies-arrayexpress
Project description:To determine whether RSPO1 and TGFβ1 activate similar transcription, RNA-seq analysis was performed to compare gene profiles after treatment by RSPO1 or TGFβ1. FET cells were treated with RSPO1 or TGFβ1 in triplicates for 4 hours and RNAs extracted from these cells were used for RNA-seq analysis. When gene expression profiles were compared, it was found that 153 genes were commonly regulated by either RSPO1 or TGFβ1. Interestingly, the majority of genes regulated by TGFβ1 were also regulated by RSPO1.
2017-09-09 | GSE103650 | GEO
Project description:Idiopathic pulmonary fibrosis is a chronic devastating disease of unknown etiology. No therapy is currently available. A growing body of evidence supports the role of TGFβ1 as the major player in the pathogenesis of the disease. This study designed novel human- and mouse-specific siRNAs and siRNA/DNA chimeras targeting both human and mouse common sequences and evaluated their inhibitory activity in pulmonary fibrosis induced by bleomycin and lung-specific transgenic expression of human TGFβ1. Selective novel sequences of siRNA and siRNA/DNA chimeras efficiently inhibited pulmonary fibrosis, indicating their applicability as tools for treating fibrotic disease in humans. Total RNA was extracted from lung tissue from mice with bleomycin (BLM)-induced lung fibrosis treated with mouse TGFβ1 siRNAs or vehicle on different days after BLM infusion.
2011-11-22 | E-GEOD-28122 | biostudies-arrayexpress