Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1313133 | ENA |
REPOSITORIES: ENA
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Project description:This study attemps to study the global effects of Serum Amyloid A (SAA) on human endothelial gene expression profile in different time points. Keywords: time course
2006-11-09 | GSE6241 | GEO
Project description:The 104 aa protein Serum Amyloid A (SAA) is a prominent member of the acute phase response (APR) a remarkably conserved and stereotyped set of serum protein changes associated with inflammation and other stimuli. N-terminal fragments of SAA can form fibrils that can accumulate in organs (“amyloidosis”). No specific biologic function has been identified for SAA; it has been considered an inert “biomarker.” In contrast to this perception of passivity, we report that exposure to both N-terminal decapeptides and intact SAA monomers can induce multiple transcripts in both enteroids and HEK293 cells. The spectrum of transcripts prominently includes proteins related to inflammation and NF-κB control, specifically NFKB1A, TNFA1P3 and IER3. SAA thus can act directly through specific transcription to alter cellular physiology with direct effects on inflammation, likely helping explain its remarkable evolutionary conservation as part of primordial defense.
2025-09-03 | GSE306801 | GEO
Project description:This study attemps to study the global effects of Serum Amyloid A (SAA) on human endothelial gene expression profile in different time points. Experiment Overall Design: HUVECs were cultured to confluence in 6-well plates and stimulated with 20 μg/ml of SAA (PeproTech) for 0, 4, 24 and 48 h. To determine the cellular transcript profile in Control (0h) and 3 different SAA groups (S4h, S24h and S48h), the relative abundance of mRNAs in SAA groups were compared with Control by use of Human Genome U133 Plus 2.0 Array (HG-U133 Plus 2.0, Affymetrix)). Each group had 2 individual samples. . In order to obtain the 3 group comparison datasets (S4h/C, S24h/C and S48h/C), expression patterns for each individual SAA sample (4h, 24h and 48h) were compared to each individual control sample. Hence, each group comparison has 4 individual sample comparisons. The robust increased or decreased cut-off was use the Affymetrix recommending "1" or "-1" of the signal log ratio. . If the gene is robust âincreasedâ or âdecreasedâ in 4 individual sample comparisons of the total 4 comparisons, it was selected as the final robust changed in group comparison. Each gene we were interested, real time PCR was carried out to validate the microarray results.
2009-04-30 | E-GEOD-6241 | biostudies-arrayexpress
Project description:Serum amyloid A (SAA) is a plasma protein that transports lipids during inflammation. To explore SAA solution conformations and lipid binding mechanism, we used hydrogen-deuterium exchange mass spectrometry, lipoprotein reconstitution, sequence analysis and molecular dynamics simulations. Solution conformations of lipid-bound and lipid-free mSAA1 at pH~7 agreed in details with the crystal structures but also showed important differences. The results revealed that amphipathic α-helices h1 and h3 comprise a lipid-binding site that is partially pre-formed in solution, is stabilized on lipoproteins, and shows lipid-induced folding of h3. This site sequesters apolar ligands via a concave hydrophobic surface in SAA oligomers. The largely disordered C-terminal region is conjectured to mediate promiscuous binding of other ligands. The h1-h2 linker region forms an unexpected β-hairpin that may represent an early amyloidogenic intermediate. The results establish structural underpinnings for understanding SAA interactions with lipids and other ligands, its evolutional conservation, and its transition to amyloid.
2020-02-17 | PXD016391 | Pride
Project description:Upon activation of ASC-containing inflammasomes, intracellular molecular aggregates (ASC specks) are assembled and released from myeloid cells into the extracellular space where they enhance the aggregation of Aβ amyloid in Alzheimer’s disease. This raises the question whether ASC is involved in additional aggregation proteinopathies. In this study we report that ASC governs the extent of inflammation-induced amyloid A (AA) amyloidosis, a systemic disease caused by the aggregation and peripheral deposition of the acute-phase reactant serum amyloid A (SAA).
2025-05-07 | PXD053372 | Pride
Project description:Vaccination reduces morbidity and mortality from pneumonia but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute phase response and lung gene expression profiles in mice inoculated intranasally with virulent gram-positive Streptococcus pneumoniae serotype (ST) 3, with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3), or co-immunization with PPS3 and with a low dose of lipopolysaccharide (LPS). Pneumonia severity was assessed in the acute phase, 5, 12, 24 and 48 h post-inoculation (p.i.) and the resolution phase of 7 days p.i. Primary PPS3 specific antibody production was upregulated and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3 + LPS decreased bacterial recovery the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole lung RNA revealed significant changes in the acute phase protein serum amyloid A (SAA) between noninfected and infected mice, which were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum, but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as co-immunization with PPS3 + LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression in the lungs, and acute phase proteins in the lungs, liver and serum. Each lung RNA sample represented an individual mouse, creating biological repeats for each treatment. In-vivo treatments were as follows: non-infected lung (vehicle-immunized) control (n=5), infected lung (vehicle-immunized) control at 48 hr post-inoculation (n=5), PPS3 and LPS co-immunized lung at 48 hr post-inoculation (n=4) and PPS3 and LPS co-immunized lung at 7 days post-inoculation (n=4).
2013-03-29 | E-GEOD-45644 | biostudies-arrayexpress
Project description:Vaccination reduces morbidity and mortality from pneumonia but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute phase response and lung gene expression profiles in mice inoculated intranasally with virulent gram-positive Streptococcus pneumoniae serotype (ST) 3, with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3), or co-immunization with PPS3 and with a low dose of lipopolysaccharide (LPS). Pneumonia severity was assessed in the acute phase, 5, 12, 24 and 48 h post-inoculation (p.i.) and the resolution phase of 7 days p.i. Primary PPS3 specific antibody production was upregulated and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3 + LPS decreased bacterial recovery the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole lung RNA revealed significant changes in the acute phase protein serum amyloid A (SAA) between noninfected and infected mice, which were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum, but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as co-immunization with PPS3 + LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression in the lungs, and acute phase proteins in the lungs, liver and serum.
2013-03-29 | GSE45644 | GEO
Project description:The liver is the most common site of metastatic disease in gastrointestinal malignancies, including pancreatic ductal adenocarcinoma (PDAC). While this metastatic tropism may reflect mechanical trapping of tumor cells that enter the circulation, liver metastasis is also dependent, at least in part, on the formation of a “pro-metastatic” niche that supports tumor cell seeding and colonization in the liver. However, mechanisms that orchestrate the establishment of this niche are poorly understood. Here, we show that hepatocytes coordinate accumulation of myeloid cells and fibrosis within the liver, the two defining features of a pro-metastatic niche. Early during pancreatic tumorigenesis in mice, hepatocytes demonstrate activation of Signal Transducer and Activator of Transcription 3 (STAT3) signaling and increased production of serum amyloid A1 and A2 (SAA). Overexpression of SAA by hepatocytes also occurs in PDAC patients with liver metastases, and many patients with locally advanced and metastatic disease display elevated levels of circulating SAA. STAT3 activation in hepatocytes and the subsequent production of SAA are dependent on interleukin 6 (IL-6) that is released into the circulation by non-malignant cells that reside adjacent to malignant cells in the pancreas. Genetic ablation or blockade of components of IL-6/STAT3/SAA signaling in hepatocytes effectively prevents the establishment of a pro-metastatic niche and inhibits metastatic seeding in the liver. Collectively, our data reveal an intercellular network underpinned by hepatocytes that forms the basis for a pro-metastatic niche in the liver and identify new therapeutic targets for pancreatic cancer.
2018-12-21 | GSE109480 | GEO
Project description:We present the 3.3 Å cryo-EM structure of an AA amyloid extracted post-mortem from the diseased kidney of a DSH cat with renal failure. The structure reveals a cross-beta architecture assembled from two 76-residue long proto-filaments. Despite >70% sequence homology to mouse and human SAA, the cat SAA variant adopts a unique amyloid fold exhibiting type-2 polymorphism. Based on shared disease profiles and almost identical sequences, we propose a similar amyloid fold of deposits identified previously in captive cheetah.
2022-11-18 | PXD035851 | Pride