Ontology highlight
ABSTRACT:
PROVIDER: PRJNA900792 | ENA |
REPOSITORIES: ENA
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Project description:Despite their emerging relevance to fully understand disease pathogenesis, we have as yet a poor understanding as to how biomechanical signals are integrated with specific biochemical pathways to determine cell behaviour. Mesothelial-to-mesenchymal transition (MMT) markers colocalized with TGF-beta1-dependent signalling and yes-associated protein (YAP) activation across biopsies from different pathologies exhibiting peritoneal fibrosis, supporting mechanotransduction as a central driving component of these class of fibrotic lesions and its crosstalk with specific signaling pathways. Transcriptome and proteome profiling of the response of mesothelial cells (MCs) to linear cyclic stretch revealed molecular changes compatible with bona fide MMT, which (i) overlapped with established YAP target gene subsets, and (ii) were largely dependent on endogenous TGF-beta1 signaling. Importantly, TGF-beta1 blockade blunts the transcriptional upregulation of the se gene signatures, but not the mechanical activation and nuclear translocation of YAP per se. We studied the role therein of caveolin-1 (Cav1), a plasma membrane mechanotransducer. Exposure of Cav1-deficient MCs to cyclic stretch led to a robust upregulation of MMT-related gene programs, which was blunted upon TGF-beta1 inhibition. Conversely, Cav1 depletion enhanced both TGF-beta1 and TGFBRI expression. Cav1 genetic deficiency exacerbated MMT and PA fibrosis in an experimental model of peritoneal ischaemic buttons. Taken together, these results support that Cav1-YAP/TAZ fine-tune the fibrotic response through the modulation of MMT, onto which TGF-beta1-dependent signaling coordinately converges. Our findings reveal a cooperation between biomechanical and biochemical signals in the triggering of MMT, representing a novel potential opportunity to intervene mechanically-induced disorders coursing with peritoneal fibrosis, such as post-surgical adhesions. This SuperSeries is composed of the SubSeries listed below.
2020-08-21 | GSE146955 | GEO
Project description:Primary open angle glaucoma (POAG) is a progressive optic neuropathy, which is a major cause of worldwide visual impairment and blindness. Pathological hallmarks of the glaucomatous optic nerve head include retinal ganglion cell axon loss and extracellular matrix (ECM) remodeling of the lamina cribrosa layer. TGF-beta is an important pro-fibrotic modulator of ECM metabolism, whose levels are elevated in human POAG lamina cribrosa tissue compared with non-glaucomatous controls. We treated human lamina cribrosa (LC) cells with TGF-beta1 (10ng/ml) for 24 hours in order to examine differential gene expression patterns in repsonse to this cytokine. In particular we focused on ECM and fibrotic genes. We found that TGF-beta1 induces expression and release of ECM components in LC cells, which may be important in regulating matrix remodeling in the lamina cribrosa. In disease states such as POAG, the LC cell may represent an important pro-fibrotic cell type and an attractive target for novel therapeutic strategies.
2008-06-12 | E-GEOD-2705 | biostudies-arrayexpress
Project description:TGF-beta1 is the major cytokine driver of fibrotic scarring observed in diabetic nephropathy and other fibrosis-related diseases. RNA-sequencing offers the potential for more sensitive assessment of the TGF-ß1-driven transcriptome.
2012-04-01 | GSE29660 | GEO
Project description:TGF-beta1-Induced Gene Expression Changes in HepG2 Cells
| PRJNA196711 | ENA
Project description:Invastigation of whole genome gene expression level changes in human osteosarcoma cell line MNNG/HOS sarcospheres,hypoxia-induced sarcospheres and TGF-beta1 induced sarcospheres. A three chip study using total RNA cover from three cultures of human osteosarcoma cell line MNNG/HOS sarcospheres, hypoxia-induced sarcospheres and TGF-beta1-induced sarcospheres. Each chip measures the expression level of 45033 genes from osteosarcoma cell line MNNG/HOS.
2012-05-22 | E-GEOD-38134 | biostudies-arrayexpress
Project description:Vascular smooth muscle cells require beta1 integrin for survival. Following the induced deletion of smooth muscle beta1 integrin, smooth muscle cells undergo apoptosis and arteries become fibrotic. This microarray study on mesenteric arteries 2 weeks after the initiation of beta1 integrin deletion specifically in smooth muscle cells of the adult mouse aimed to examine early changes in expression following deletion.
2013-02-26 | GSE44663 | GEO
Project description:Invastigation of whole genome gene expression level changes in human osteosarcoma cell line MNNG/HOS sarcospheres,hypoxia-induced sarcospheres and TGF-beta1 induced sarcospheres.
2012-05-23 | GSE38134 | GEO
Project description:TGF-beta1-Induced Gene Expression Changes in Primary Murine Hepatocytes
| PRJNA196710 | ENA
Project description:Vascular smooth muscle cells require beta1 integrin for survival. Following the induced deletion of smooth muscle beta1 integrin, smooth muscle cells undergo apoptosis and arteries become fibrotic. This microarray study on mesenteric arteries 2 weeks after the initiation of beta1 integrin deletion specifically in smooth muscle cells of the adult mouse aimed to examine early changes in expression following deletion. Mesenteric arteries from three wild type mixed background and three beta1 integrin smooth muscle knockout mixed background mice are examined.
2013-02-26 | E-GEOD-44663 | biostudies-arrayexpress
Project description:Primary open angle glaucoma (POAG) is a progressive optic neuropathy, which is a major cause of worldwide visual impairment and blindness. Pathological hallmarks of the glaucomatous optic nerve head include retinal ganglion cell axon loss and extracellular matrix (ECM) remodeling of the lamina cribrosa layer. TGF-beta is an important pro-fibrotic modulator of ECM metabolism, whose levels are elevated in human POAG lamina cribrosa tissue compared with non-glaucomatous controls. We treated human lamina cribrosa (LC) cells with TGF-beta1 (10ng/ml) for 24 hours in order to examine differential gene expression patterns in repsonse to this cytokine. In particular we focused on ECM and fibrotic genes. We found that TGF-beta1 induces expression and release of ECM components in LC cells, which may be important in regulating matrix remodeling in the lamina cribrosa. In disease states such as POAG, the LC cell may represent an important pro-fibrotic cell type and an attractive target for novel therapeutic strategies. Keywords: other
2005-08-05 | GSE2705 | GEO