Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Severe infection constitutively upregulates TIMP1 in the bone marrow hematopoietic niche to support long-term enhanced myelopoiesis

ABSTRACT: Severe infection constitutively upregulates TIMP1 in the bone marrow hematopoietic niche to support long-term enhanced myelopoiesis

PROVIDER: PRJNA847242 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR19589068.fastq.gz	Fastqsanger.gz
	SRR19589069.fastq.gz	Fastqsanger.gz

Items per page:

1 - 2 of 2

Similar Datasets

Severe infection constitutively upregulates TIMP1 in the bone marrow hematopoietic niche to support long-term enhanced myelopoiesis

Project description:Infection is able to elicit innate immunological memory by enhancing a long-term myeloid output even after the inciting infectious agent has been cleared. However, mechanisms underlying such a regulation are not fully understood. Using a mouse polymicrobial peritonitis (sepsis) model, we show that severe infection leads to increased, sustained myelopoiesis after the infection is resolved. The infection experience is imprinted in the bone marrow (BM) stromal cells, in the form of a constitutive upregulation of the tissue inhibitor of metalloproteinases 1 (TIMP1). TIMP1 antagonizes the function of ADAM10, an essential cleavage enzyme for the activation of Notch which in turn suppresses myelopoiesis. While TIMP1 is dispensable for myelopoiesis under the steady state, increased TIMP1 enhances myelopoiesis post infection. Thus, our data reveal that infection could establish an inflammatory memory in the BM niche to support a long-term enhanced output of innate immune cells.

2022-06-15 | GSE205728 | GEO

TIMP1 overexpression mediates resistance of MCF-7 human breast cancer cells to fulvestrant and down-regulates progesterone receptor expression

Project description:High levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP1) are associated with poor prognosis, reduced response to chemotherapy, and, potentially, also poor response to endocrine therapy in breast cancer patients. Our objective was to further investigate the hypothesis that TIMP1 is associated with endocrine sensitivity. We established a panel of 11 MCF-7 subclones with a wide range of TIMP1 mRNA and protein expression levels. Cells with high expression of TIMP1 versus low TIMP1 displayed significantly reduced sensitivity to the antiestrogen fulvestrant (ICI 182,780, Faslodex®), while TIMP1 levels did not influence the sensitivity to 4-hydroxytamoxifen. An inverse correlation between expression of the progesterone receptor and TIMP1 was found, but TIMP1 levels did not correlate with estrogen receptor levels or growth-promoting effects of estrogen (estradiol, E2). Additionally, the effects of fulvestrant, 4-hydroxytamoxifen, or estrogen on estrogen receptor expression were not associated with TIMP1 levels. Gene expression analyses revealed associations between expression of TIMP1 and genes involved in metabolic pathways, epidermal growth factor receptor 1/cancer signaling pathways, and cell cycle. Gene and protein expression analyses showed no general defects in estrogen receptor signaling except from lack of progesterone receptor expression and estrogen inducibility in clones with high TIMP1. The present study suggests a relation between high expression level of TIMP1 and loss of progesterone receptor expression combined with fulvestrant resistance. Our findings in vitro may have clinical implications as the data suggest that high tumor levels of TIMP1 may be a predictive biomarker for reduced response to fulvestrant.

2013-08-22 | GSE35535 | GEO

TIMP1 overexpression mediates resistance of MCF-7 human breast cancer cells to fulvestrant and down-regulates progesterone receptor expression

Project description:High levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP1) are associated with poor prognosis, reduced response to chemotherapy, and, potentially, also poor response to endocrine therapy in breast cancer patients. Our objective was to further investigate the hypothesis that TIMP1 is associated with endocrine sensitivity. We established a panel of 11 MCF-7 subclones with a wide range of TIMP1 mRNA and protein expression levels. Cells with high expression of TIMP1 versus low TIMP1 displayed significantly reduced sensitivity to the antiestrogen fulvestrant (ICI 182,780, FaslodexÂ®), while TIMP1 levels did not influence the sensitivity to 4-hydroxytamoxifen. An inverse correlation between expression of the progesterone receptor and TIMP1 was found, but TIMP1 levels did not correlate with estrogen receptor levels or growth-promoting effects of estrogen (estradiol, E2). Additionally, the effects of fulvestrant, 4-hydroxytamoxifen, or estrogen on estrogen receptor expression were not associated with TIMP1 levels. Gene expression analyses revealed associations between expression of TIMP1 and genes involved in metabolic pathways, epidermal growth factor receptor 1/cancer signaling pathways, and cell cycle. Gene and protein expression analyses showed no general defects in estrogen receptor signaling except from lack of progesterone receptor expression and estrogen inducibility in clones with high TIMP1. The present study suggests a relation between high expression level of TIMP1 and loss of progesterone receptor expression combined with fulvestrant resistance. Our findings in vitro may have clinical implications as the data suggest that high tumor levels of TIMP1 may be a predictive biomarker for reduced response to fulvestrant. Microarray analysis of total RNA from 10 subclones of MCF-7 breast cancer cells with various expression levels of TIMP1.

2013-08-22 | E-GEOD-35535 | biostudies-arrayexpress

Effect of TIMP1 treatment on human VSMC gene expression

Project description:Human VSMC isolates generated from aortic explants were treated in serum free media, +/- the addition of 500 ng / mL TIMP1 for 6 hours

2024-04-09 | GSE246647 | GEO

Efferocytosis fuels malignant pleural effusion through TIMP1

Project description:Malignant Pleural Effusion (MPE) results from the capacity of several human cancers to metastasize to the pleural cavity. The median survival is 3-12 months and no effective treatments are currently available. Immune-based therapies have failed until now, reflecting our insufficient understanding of the basic immunological mechanisms leading to MPE progression. Here, we show that phagocytosis of apoptotic cells in the pleural cavity fuels the progression of MPE. We found that efferocytosis through the receptor tyrosine kinases AXL and MERTK in macrophages led to the production of IL-10. Using single cell RNA-Seq, we revealed that IL-10 is indeed produced by four distinct pleural cavity macrophage subpopulations characterized by different metabolic states and cell chemotaxis properties. In turn, IL-10 acts on dendritic cells (DCs) inducing the production of tissue inhibitor of metalloproteinases 1 (TIMP1). Genetic ablation of AXL and MERTK in macrophages or IL-10 receptor in DCs or TIMP1 significantly reduced MPE progression. Taken together, our results delineate an inflammatory cascade – from the clearance of apoptotic cells by macrophages, to production of IL-10, to induction of TIMP1 in DCs – that facilitates MPE progression. This inflammatory cascade offers a series of targets for therapies which aim at preventing or treating MPE.

2021-08-24 | GSE172455 | GEO

Efferocytosis fuels malignant pleural effusion through TIMP1

Project description:Efferocytosis fuels malignant pleural effusion through TIMP1

| PRJNA723335 | ENA

SM004 - SARS infection of C57BL6, TIMP1 and Serpine1 knock-out mice.

Project description:This purpose of this experiment was to investigate the transcriptional differences between C57BL6, TIMP1 and Serpine1 knock-out mice infected with SARS MA15 virus. Overview of Experiment: Groups of 20 week old C57BL6, TIMP1 and Serpine1 (PAI1) knock-out mice were infected with SARS MA15 virus. Infections were done at 10^4 PFU or time-matched mock infected. Time points were 4 and 7 d.p.i. There were 2-4 animals/dose/time point. Lung samples were collected for virus load, transcriptional and proteomics analysis. Weight loss and animal survival were also monitored.

2014-02-20 | E-GEOD-51386 | biostudies-arrayexpress

SM004 - SARS infection of C57BL6, TIMP1 and Serpine1 knock-out mice.

Project description:This purpose of this experiment was to investigate the transcriptional differences between C57BL6, TIMP1 and Serpine1 knock-out mice infected with SARS MA15 virus.

2014-02-20 | GSE51386 | GEO

Systemic Inflammation Impairs Human Myelopoiesis

Project description:Systemic Inflammation Impairs Human Myelopoiesis

| PRJNA873943 | ENA

Effect of TIMP1 depletion on gene expression in MIA PaCa-2 cell line by CRISPR/Cas9-based targeting of exon 4

Project description:This is a bulk RNA sequencing dataset of MIA PaCa-2 cells with or without genetic manipulation of the TIMP1 gene. A two-guide RNA system was used and designed to target two sites of exon 4, introducing a 64-bp deletion, leading to a frameshift and premature stop-codon. This led to the generation of two TIMP1 KO cell lines, as well as a CRISPR control cell line that acquired only a silent point mutation (g.64C>T) without altering the amino acid sequence. To measure the impact of TIMP1 on MIA PaCa-2 gene expression, bulk RNAseq was performed for all four cell lines (WT, CRISPR Control, KO 1, and KO 2) in triplicates.

2025-11-25 | GSE290413 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data