YAP mediates TNF effect on pro-fibrotic genes expression
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA799310 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:YAP/TAZ are transcription co-factors recently described responsive to pro-inflammatory cytokines and involved in inflammatory-related disorders. However, the role of tumor necrosis factor (TNF), a major pro-inflammatory cytokine, on YAP signaling is not well understood and controversial. Here, we observe in vitro, using wild type and YAP knockout HEK293 cells, that TNF triggers YAP nuclear translocation and transcriptional activity, thus being dependent on Rho family of GTPases. In response to TNF, YAP transcriptional activity orientates cell fate toward survival. Transcriptional analysis with Nanostring technology reveals that YAP modulates TNF-induced increase in fibro-inflammatory pathways such as NF-κB, inflammasomes, cytokines or chemokines signaling as well as pro-fibrotic pathways involving TGF-β and extracellular matrix remodeling. Therefore, in response to TNF, YAP acts as a sustainer of the inflammatory response and as a molecular link between inflammation and fibrotic processes. This work identifies that YAP is critical to drive several biological effects of TNF which are involved in cancer and inflammatory disorders.
2022-03-09 | GSE194136 | GEO
Project description:Objective: To evaluate gene expression profiles in patients with advanced cirrhosis compared with healthy controls (HC). Results: Patients with advanced cirrhosis exhibit an unbalanced systemic response involving pro-fibrotic / protective signatures that could be contributing to the pathogenesis of cirrhosis and also to that of the extra-hepatic complications of this disease.
2016-02-14 | E-MTAB-3338 | biostudies-arrayexpress
Project description:Epoxygenases belong to the cytochrome P450 family and they generate epoxyeicosatrienoic acids (EETs) known to have anti-inflammatory effects but little is known about their role in macrophage function. By high-throughput sequencing of RNA (RNA-seq) in primary macrophages derived fromrodents and humans, we establish the relative expression of epoxygenases in these cells. Zinc-finger nuclease-mediated targeted gene deletion of the major rat macrophage epoxygenase Cyp2j4 (orthologue of human CYP2J2),resulted inreduced EET synthesis. Cyp2j4-/-macrophages have relatively increased PPARγ levels and show a pro-fibrotic transcriptome,displayingover-expression of a specific subset of genes (260 transcripts) primarily involved in extracellular matrix, with fibronectin being the most abundantly expressed transcript.Fibronectin expression is under the control of epoxygenase activity in human and rat primary macrophages. In keeping with the invitro findings, Cyp2j4-/- rats show up-regulation of type I collagen following unilateral ureter obstruction (UUO) of the kidney and quantitative proteomics analysis (LC-MS/MS) showed increased renal type I collagen and fibronectin protein abundance resulting from experimentally induced crescentic glomerulonephritis in these rats. Taken together, these results identify the rat epoxygenase Cyp2j4 as a determinant of a pro-fibrotic macrophage transcriptome that could have implications in various inflammatory conditions depending on macrophage function. Gene expression profile generated for macrophages in wild type and Cyp2j4 KO WKY rats
2015-02-10 | E-GEOD-65715 | biostudies-arrayexpress
Project description:IL-5 increases pro-fibrotic and pro-inflammatory signalling in severe asthmatic fibroblasts
| PRJNA1203681 | ENA
Project description:ImportanceChronic or repeated infection of the female upper genital tract by C. trachomatis can lead to severe fibrotic sequelae, including tubal factor infertility and ectopic pregnancy. However, the molecular mechanisms underlying this effect are unclear. In this report, we define a transcriptional program specific to C. trachomatis infection of the upper genital tract, identifying tissue-specific induction of host YAP-a pro-fibrotic transcriptional cofactor-as a potential driver of infection-mediated fibrotic gene expression. Furthermore, we show that infected endocervical epithelial cells stimulate collagen production by fibroblasts and implicate chlamydial induction of YAP in this effect. Our results define a mechanism by which infection mediates tissue-level fibrotic pathology via paracrine signaling and identify YAP as a potential therapeutic target for the prevention of Chlamydia-associated scarring of the female genital tract.
| S-EPMC10734534 | biostudies-literature
Project description:Fibrosis is a hallmark feature of airway remodeling in asthma. However, the exact molecular mechanisms driving its development and progression remain inadequately understood. Interleukin-5 (IL-5) plays a potent role in the inflammatory response associated with eosinophils and asthma pathophysiology, but its direct impact on lung fibroblasts and contribution to fibrosis have yet to be fully explored. In our study, we investigated the pro-fibrotic effects of IL-5 on human lung fibroblasts derived from asthmatic and normal subjects. Following IL-5 stimulation, these fibroblasts were subjected to a series of experiments to assess IL-5’s impact on fibrosis. Our findings reveal that IL-5 triggers the release of several extracellular matrix (ECM) components, and disrupts the balance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) . This imbalance further disrupts the MMP/TIMP ratio. Additionally, IL-5 stimulation promotes the release of pro-inflammatory and pro-fibrotic cytokines, Overall, these findings indicate a novel pro-fibrotic role of IL-5 through its direct action on lung fibroblasts, offering valuable insights into the therapeutic potential of targeting IL-5 to mitigate or possibly reverse airway remodeling in asthma.
2025-04-11 | GSE285468 | GEO
Project description:Myeloid cells are critical to the development of fibrosis following muscle injury, however, the mechanism of their role in fibrosis formation remains unclear. Here we demonstrate that myeloid cell-derived TGF-β1 signaling is increased in a pro-fibrotic ischemia-reperfusion and cardiotoxin (IR/CTX) muscle injury model. This study analyzes scRNAsequencing from the fibrotic region after a pro-fibrotic ischemia-reperfusion and cardiotoxin muscle injury.
2020-01-28 | GSE144270 | GEO
Project description:Pro-fibrotic and pro-inflammatory genes driven by steroid hormone imbalance in the prostate
| PRJNA909775 | ENA
Project description:Microprotein-Encoding RNA Regulation in Cells Treated with Pro-inflammatory and Pro-Fibrotic Stimuli
| PRJNA1121277 | ENA
Project description:Conversion of cardiospheres derived primitive cardiac stromal cells into myofibroblasts is typically associated with hypoxia conditions, metabolic insults, and/or inflammation, all of which are predisposing factors to cardiac fibrosis and heart failure. We hypothesized that this conversion could be also mediated by response of these cells to mechanical cues through activation of the Hippo transcriptional pathway. The objective of the present study was to assess the role of cellular/nuclear straining forces acting in myofibroblast differentiation of cardiospheres derived primitive cardiac stromal cells under the control of YAP transcription factor and to validate this finding using a pharmacological agent that interferes with the interactions of the YAP/TAZ complex with their cognate transcription factors TEADs, under high-strain and pro-fibrotic stimulation. We employed high content imaging, 2D/3D culture, atomic force microscopy mapping and molecular methods to prove the role of cell/nuclear straining in YAP-dependent fibrotic programming in a mouse model of ischemia-dependent cardiac fibrosis and in human-derived primitive cardiospheres derived primitive cardiac stromal cells . We also tested treatment of cells with Verteporfin, a drug known to prevent the association of the YAP/TAZ complex with their cognate transcription factors TEADs. Results suggested that pharmacologically targeting the YAP-dependent pathway overrides the pro-fibrotic activation of cardiospheres derived primitive cardiac stromal cells by mechanical cues in vitro, and that this occurs even in the presence of pro-fibrotic signaling mediated by TGF-β1. In vivo administration of Verteporfin in mice with permanent cardiac ischemia reduced significantly fibrosis and morphometric remodeling but did not improve cardiac performance. Our study indicates that preventing molecular translation of mechanical cues in cardiospheres derived primitive cardiac stromal cells reduces the impact of cardiac maladaptive remodeling with a positive effect on fibrosis.
2022-06-30 | GSE203358 | GEO