GPI-anchored Timp1 protein
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE40301 | GEO | 2012/08/23
SECONDARY ACCESSION(S): PRJNA173439
REPOSITORIES: GEO
Similar Datasets
Project description:Tissue inhibitor of metalloproteinase 1 (TIMP-1) controls matrix metalloproteinase (MMP) activity through 1:1 stochiometric binding. Human TIMP-1 fused to a glycosylphosphatidylinositol (GPI) anchor (TIMP-1-GPI) shifts the activity of TIMP-1 from the extracellular matrix to the cell surface. TIMP-1-GPI treated renal cell carcinoma cells (RCC) show increased apoptosis and reduced proliferation. Transcriptomic profiling and regulatory pathway mapping were used to identify potential mechanisms driving these effects. Significant changes in inhibitor of DNA binding (IDs), TGF-β1/SMAD and BMP pathways resulted from TIMP-1-GPI treatment. These events were linked to reduced TGF-β1 signaling mediated by inhibition of proteolytic processing of latent TGF-β1 by TIMP-1-GPI. Activity of TIMP-1 from the extracellular matrix to the cell surface. TIMP-1-GPI treated renal cell carcinoma cells (RCC) show increased apoptosis and reduced proliferation. Transcriptomic profiling and regulatory pathway mapping were used to identify potential mechanisms driving these effects. Significant changes in inhibitor of DNA binding (IDs), TGF-β1/SMAD and BMP pathways resulted from TIMP-1-GPI treatment. These events were linked to reduced TGF-β1 signaling mediated by inhibition of proteolytic processing of latent TGF-β1 by TIMP-1-GPI. Renal cell carcinoma cells were transfected with empty vector, rhTimp1 and 2 concentrations of Timp1-GPI fusion protein
2012-08-23 | E-GEOD-40301 | biostudies-arrayexpress
Project description:Increased levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) have been detected in fibrotic strictures in Crohn’s disease. In a murine model of chronic inflammation, fibrosis was associated with an increase in TIMP-1 and inhibition of matrix metalloproteinase (MMP)-mediated degradation. We investigated the effect of TIMP-1 deficiency on the colonic gene expression in acute and chronic murine models of colitis, using whole genome gene expression arrays.
2016-07-22 | GSE73424 | GEO
Project description:Venkatraman2012 - Interplay between PLS and TSP1 in TGF-β1 activation
The interplay between PLS (Plasmin) and TSP1 (Thrombospondin-1) in TGF-β1 (Transforming growth factor-β1)is shown using mathematical modelling and in vitro
experimentents.
This model is described in the article:
Plasmin triggers a switch-like decrease in thrombospondin-dependent activation of TGF-β1.
Venkatraman L, Chia SM, Narmada BC, White JK, Bhowmick SS, Forbes Dewey C Jr, So PT, Tucker-Kellogg L, Yu H.
Biophys J. 2012 Sep 5;103(5):1060-8.
Abstract:
Transforming growth factor-β1 (TGF-β1) is a potent regulator of extracellular matrix production, wound healing, differentiation, and immune response, and is implicated in the progression of fibrotic diseases and cancer. Extracellular activation of TGF-β1 from its latent form provides spatiotemporal control over TGF-β1 signaling, but the current understanding of TGF-β1 activation does not emphasize cross talk between activators. Plasmin (PLS) and thrombospondin-1 (TSP1) have been studied individually as activators of TGF-β1, and in this work we used a systems-level approach with mathematical modeling and in vitro experiments to study the interplay between PLS and TSP1 in TGF-β1 activation. Simulations and steady-state analysis predicted a switch-like bistable transition between two levels of active TGF-β1, with an inverse correlation between PLS and TSP1. In particular, the model predicted that increasing PLS breaks a TSP1-TGF-β1 positive feedback loop and causes an unexpected net decrease in TGF-β1 activation. To test these predictions in vitro, we treated rat hepatocytes and hepatic stellate cells with PLS, which caused proteolytic cleavage of TSP1 and decreased activation of TGF-β1. The TGF-β1 activation levels showed a cooperative dose response, and a test of hysteresis in the cocultured cells validated that TGF-β1 activation is bistable. We conclude that switch-like behavior arises from natural competition between two distinct modes of TGF-β1 activation: a TSP1-mediated mode of high activation and a PLS-mediated mode of low activation. This switch suggests an explanation for the unexpected effects of the plasminogen activation system on TGF-β1 in fibrotic diseases in vivo, as well as novel prognostic and therapeutic approaches for diseases with TGF-β dysregulation.
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2013-03-26 | BIOMD0000000447 | BioModels
Project description:Increased levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) have been detected in fibrotic strictures in Crohnâs disease. In a murine model of chronic inflammation, fibrosis was associated with an increase in TIMP-1 and inhibition of matrix metalloproteinase (MMP)-mediated degradation. We investigated the effect of TIMP-1 deficiency on the colonic gene expression in acute and chronic murine models of colitis, using whole genome gene expression arrays. Colitis was induced via oral administration of dextran sodium sulphate (DSS) to B6.129S4-Timp1tm1Pds/J knock-out (KO) and C57BL/6J wild-type (WT) mice. Total RNA extracted from snap frozen colon was used to analyze mRNA expression via Affymetrix Mouse Gene 1.0 ST Arrays
2016-07-22 | E-GEOD-73424 | biostudies-arrayexpress
Project description:Fibrotic diseases have significant health impact and have been associated with differentiation of the resident fibroblasts into myofibroblasts. In particular, stiffened extracellular matrix and TGF-β1 in fibrotic lesions have been shown to promote pathogenic myofibroblast activation and progression of fibrosis in various tissues. To better understand the roles of mechanical and chemical cues on myofibroblast differentiation and how they may crosstalk, we cultured primary valvular interstitial cells (VICs) isolated from porcine aortic valves and studied how traditional TCPS culture, which presents a non-physiologically stiff environment, and TGF-β1 affect native VIC phenotypes. We carried out gene expression profiling using porcine genome microarrays from Affymetrix and found that traditional TCPS culture induces major changes in gene expression of native VICs, rendering these cells more activated and similar to cells treated with TGF-β1. We also monitored time-dependent effects induced by TGF-β1 by examining gene expression changes induced by TGF-β1 at 8 hours and 24 hours. Porcine aortic VICs were isolated and cultured with or without TGF-β1 treatment for RNA extraction and hybridization on Affymetrix microarrays. We included 3 biological replicates for each condition. P0 VICs were freshly isolated cells which had not been cultured. P2 VICs were cells that had been passaged 2 times and cultured on plastic plates in low serum media. Some of the P2 VICs were treated with TGF-β1 at 5ng/ml for 8 hours or 24 hours. All the control and TGF-β1-treated conditions were collected at the same time on day 3 of culture.
2013-09-02 | E-GEOD-48839 | biostudies-arrayexpress
Project description:Matrix metalloproteinase-9 and TIMP-1 in peripheral nerve: Implications for myelin formation
| PRJNA148677 | ENA
Project description:In this study, we examined the impact of modulating the TGF-β/PAI-1 axis in CD34+ cells function from diabetic patients and controls. Using gene array studies, we found that diabetics, protected from microvascular complications despite suboptimal glycemic control, had reduced level of TGF- β1 and PAI-1 transcripts in their CD34+ cells compared to age, sex, duration and degree of glycemic control -matched diabetics with microvascular complications. Treatment with neutralizing antibody to TGF- β1 in murine hematopoietic stem cells (HSC) enhanced in vivo repopulation potential of these cells in bone marrow transplantation; reduced the time required for cell division of single cells, increased survival of the progenitor cells and reduced TGF-β1 expression. TGF- β1 phosphorodiamidate morpholino oligomers (PMO) treatment reduced PAI-1 mRNA expression in diabetic (p<0.01) and non-diabetic (p=0.05) CD34+ cells. Inhibition of PAI-1 promoted CD34+ cell proliferation and migration in vitro.Targetting TGFβ-1/PAI-1 system offers a promising therapeutic strategy for restoring vascular reparative function in diabetic CD34+ cells and hematopoietic stem cells, enhancing key functions needed for cell therapy. Peripheral blood from either age matched controls (n=5), diabetics with long standing poorly controlled diabetes and no microvascular complications (n=4), and diabetics with long-standing poorly controlled diabetes with severe microvascular complications (n=5) was obtained and CD34+ cells were isolated. RNA was extracted followed by AffyNugen amplification, and the cDNA was probed to Human RSTA Affymetrix 2.0 chip
2013-02-01 | E-GEOD-43950 | biostudies-arrayexpress
Project description:Members of the NADPH oxidase (NOX) family of enzymes, which catalyze the reduction of O2 to reactive oxygen species, have increased in number during eukaryotic evolution. Seven isoforms of the NOX gene family have been identified in mammals; however, specific roles of NOX enzymes in mammalian physiology and pathophysiology have not been fully elucidated. The best established physiological role of NOX enzymes is in host defense against pathogen invasion in diverse species, including plants. The prototypical member of this family, NOX-2 (gp91phox), is expressed in phagocytic cells and mediates microbicidal activities. Here we report a role for the NOX4 isoform in tissue repair functions of myofibroblasts and fibrogenesis. Transforming growth factor-β1 (TGF-β1) induces NOX-4 expression in lung mesenchymal cells by a SMAD-3–dependent mechanism. NOX-4–dependent generation of hydrogen peroxide (H2O2) is required for TGF-β1–induced myofibroblast differentiation, extracellular matrix (ECM) production and contractility. NOX-4 is upregulated in lungs of mice subjected to noninfectious injury and in cases of human idiopathic pulmonary fibrosis (IPF). Genetic or pharmacologic targeting of NOX-4 abrogates fibrogenesis in two murine models of lung injury. These studies support a function for NOX4 in tissue fibrogenesis and provide proof of concept for therapeutic targeting of NOX-4 in recalcitrant fibrotic disorders. Experiment Overall Design: mRNA expression of genes in human fetal lung mesenchymal cells (IMR-90) treated with or without TGF-β1, as analyzed by Affymetrix (U133A) microarrays. Control (C0, C2, C3) = cells without TGF-β1 treatment (n=3). Experimental (T0, T5, T7) = cells treated with TGF-β1 (2ng/ml) (n=3). mRNA was collected for all 6 samples for 48 hours post treatment.
2009-08-25 | E-GEOD-17518 | biostudies-arrayexpress
Project description:We studied miRNAs and their gene targets affecting SARS-CoV-2 pathogenesis in CF airway epithelial cell models in response to TGF-β1. Small RNAseq in CF human bronchial epithelial cell line treated with TGF-β1 and miRNA profiling characterized TGF-β1 effects on the SARS-CoV-2 pathogenesis pathways. Among the effectors, we identified and validated two miRNAs targeting ACE2 mRNA using different CF and non-CF human bronchial epithelial cell models. We have shown that TGF-β1 inhibits ACE2 expression by miR-136-3p and miR-369-5p. ACE2 levels were higher in cells expressing F508del-CFTR, compared to wild-type(WT)-CFTR and TGF-β1 inhibited ACE2 in both cell types. The ACE2 protein levels were still higher in CF, compared to non-CF cells after TGF-β1 treatment. TGF-β1 prevented the functional rescue of F508del-CFTR by ETI in primary human bronchial epithelial cells while ETI did not prevent the TGF-β1 inhibition of ACE2 protein. Finally, TGF-β1 reduced binding of ACE2 to the recombinant monomeric spike RBD. Our results may help to explain, at least in part, the role of TGF-β1 on the SARS-CoV-2 entry via ACE2 in the CF and non-CF airway.
2023-04-01 | GSE226758 | GEO
Project description:The etiology of autoimmune hepatitis is poorly understood but likely involves Th1 cells producing IFN-γ. BALB/c background TGF-β1-/- mice rapidly develop fulminant Th1-mediated autoimmune hepatitis. Our aims are to profile liver gene expression in TGF-β1-/- mice, to identify gene expression pathways dependent on IFN-γ as possible targets for rational therapy, and to test potential targets directly in vivo in mice. Keywords: Comparative analysis of gene expression in livers of WT, TGFB1 & IFN knockout mice DNA microarray analyses were applied to liver RNA from TGF-β1-/- mice, TGF-β1-/- /IFN-γ-/- mice, and TGF-β1+/+ littermate controls. 3 mice from each group were analyzed in this study.
2009-02-28 | E-GEOD-9892 | biostudies-arrayexpress