Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA272714 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:TGFβ inhibition attenuates chronic cigarette smoke induced lung injury and rescues lung architecture.
2011-12-30 | GSE33561 | GEO
Project description:Transforming growth factor β (TGFβ) signaling is a core pathway of fibrosis, but the molecular regulation of the activation of latent TGFβ remains incompletely understood. Here, we demonstrate a crucial role of WNT5A/JNK/ROCK signaling that rapidly coordinates the activation of latent TGFβ in fibrotic diseases. WNT5A was identified as predominant non-canonical WNT ligand in fibrotic diseases such as systemic sclerosis, sclerodermatous chronic graft-versus-host disease and idiopathic pulmonary fibrosis, stimulating fibroblast-to-myofibroblast transition and tissue fibrosis by activation of latent TGFβ. The activation of latent TGFβ requires rapid JNK- and ROCK-dependent cytoskeletal rearrangements and integrin αV (ITGAV). Conditional Knockout of WNT5A or its downstream targets prevented activation of latent TGFβ, rebalanced TGFβ signaling and ameliorated experimental fibrosis. We thus uncovered a novel mechanism for the aberrant activation of latent TGFβ in fibrotic diseases and provided evidence for targeting WNT5A/JNK/ROCK signaling in fibrotic diseases as a new therapeutic approach.
2024-02-29 | GSE222916 | GEO
Project description:Radiation-induced pulmonary fibrosis (RIPF) is one of the most common side effects of lung cancer radiotherapy. In the mouse lungs developing RIPF, excessive accumulation of extracellular matrix and myofibroblasts with scar formation occurs. We used microarrays to detail the global program of gene expression underlying development of radiation-induced pulmonary fibrosis and identified a variety of genes whose expression were up-regulated during this process.
2017-01-12 | GSE93410 | GEO
Project description:The platelet-derived growth factor (PDGF) signaling system contributes to tumor angiogenesis and vascular remodeling. Here, we show PDGF-BB markedly induces erythropoietin (EPO) mRNA and protein expression by targeting the PDGFR-beta+ stromal and perivascular compartments. In mouse tumor models, PDGF-BB-induced EPO promotes tumor growth via two mechanisms: 1) paracrine stimulation of tumor angiogenesis by directly inducing endothelial cell proliferation, migration, sprouting and tube formation; and 2) endocrine stimulation of extramedullary hematopoiesis leading to increased oxygen perfusion and protection against tumor-associated anemia. Similarly, delivery of an adenovirus-PDGF-BB to tumor-free mice markedly increases EPO production and hematopoietic parameters. An EPO blockade specifically attenuates PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. At the molecular level, we show that the PDGF-BB-PDGFR-beta signaling system activates EPO promoter via in part transcriptional regulation of ATF3 by possible association with c-Jun and SP1. These findings uncover a novel mechanism of PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. Comparison of S17 stromal cells treated with PDGF-BB for 72h to control
2011-12-04 | E-GEOD-33717 | biostudies-arrayexpress
Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic and often fatal pulmonary disorder characterized by fibroblast proliferation and the excess deposit of extracellular matrix proteins. The etiology of IPF is unknown, but a central role for microRNAs (miRNAs), a class of small non-coding regulatory RNAs, has been recently suggested. We report the upregulation of miR-199a-5p in mouse lungs undergoing bleomycin-induced fibrosis and also in human biopsies from IPF patients. Levels of miR-199a-5p were increased selectively in myofibroblasts and putative profibrotic effects of miR-199a-5p were further investigated in cultured lung fibroblasts. MiR-199a-5p expression was induced upon TGFβ exposure and ectopic expression of miR-199a-5p was sufficient to promote the pathogenic activation of pulmonary fibroblasts. CAV1, a critical mediator of pulmonary fibrosis, was established as a bona fide target of miR-199a-5p. Finally, we also found an aberrant expression of miR-199a-5p in mouse models of kidney and liver fibrosis, suggesting that dysregulation of miR-199a-5p represents a general mechanism contributing to the fibrotic process. We propose miR-199a-5p as a major regulator of fibrosis that represents a potential therapeutic target to treat fibroproliferative diseases. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-02-01 | E-GEOD-34818 | biostudies-arrayexpress
Project description:Radiotherapy is standard of care for inoperable non-small cell lung cancers (NSCLC) but adenocarcinoma NSCLC respond more poorly than squamous cell NSCLC. Transforming growth factor β (TGFβ) activity is induced by radiation and plays a recently recognized role in the DNA damage response. Here we show in murine lung tumor model that radiation activates TGFβ acutely and persistently and that TGFβ neutralizing antibody, 1D11, systemic treatment increased tumor control following either fractionated or single high dose radiation regimes. TGFβ dependent genes in the irradiated tumor indicated crosstalk between innate and adaptive immunity but therapeutic benefit of 1D11 in irradiated tumors in immunocompromised mice suggested that innate immune cells are more influential than the adaptive immune response. Irradiated tumors in which TGFβ was blocked were highly hypoxic, exhibit pronounced microvascular damage and promoted neither cancer-associated fibroblasts nor recruit bone marrow derived cells (BMDC). Tumor educated immature BMDC were significant sources of TGFβ and inhibiting BMDC recruitment achieved tumor growth control in response to RT comparable to TGFβ inhibition. Thus, radiation-induced TGFβ both compromises tumor control by RT and promotes reestablishment of the tumor microenvironment. Concordant with the critical role of TGFβ activity in RT, radiation resistant NSCLC adenocarcinomas exhibit higher TGFβ activity compared to squamous cell NSCLC, which suggests a rationale for using TGFβ inhibition to augment radiotherapy.
2015-12-15 | GSE73095 | GEO
Project description:TGFβ inhibition attenuates chronic cigarette smoke induced lung injury and rescues lung architecture. AKR/J mice were exposed to Cigarette Smoke (CS) for a period of two months. Some animals received a treatment of Losartan (.6gr/L) orally while exposed (CS Los). These two groups are to be compared to animals that remained in Room Air (RA) and Room Air plus Losartan(0.6g/L) (RA Los) for any changes.
2011-12-30 | E-GEOD-33561 | biostudies-arrayexpress
Project description:Radiation Induced Lung Injury (RILI) is one of the main limiting factors of thorax irradiation, which can induce acute pneumonitis as well as pulmonary fibrosis, the latter being a life-threatening condition. The order of cellular and molecular events in the progression towards fibrosis is key to the physiopathogenesis of the disease, yet their coordination in space and time remains largely unexplored. Here, we present an interactive murine single cell atlas of the lung responses to irradiation. This analysis opens the door for exploration of the spatio-temporal dynamics of the mechanisms that lead to radiation-induced pulmonary fibrosis. It depicts with unprecedented detail cell type-specific radiation-induced responses associated with either lung regeneration or the failure thereof. A better understanding of the mechanisms leading to lung fibrosis will help finding new therapeutic options that could improve patients’ quality of life.
2023-03-20 | GSE211713 | GEO
Project description:Expression data from radiation-induced pulmonary fibrosis mouse models
| PRJNA360918 | ENA