Similar Datasets
Project description:Physiologically, albumin is produced by hepatocytes. It remains largely unknown how patients are capable of maintaining essential albumin levels even in the condition of liver failure. Here, we delineate a hierarchical regulatory network that controls albumin transcription under different pathophysiological conditions. The ALB core promoter possesses a TATA box and nucleosome-free area, which allows constitutive binding of RNA Pol II and thus initiation of transcription. In normal conditions, HNF4α and C/EBPα facilitate albumin transcription through binding to its promoter. In severely damaged livers, hepatocellular HNF4α and C/EBPα expression is often inhibited. The absence of HNF4 and C/EBPα increases hedgehog ligand biosynthesis. Hedgehog upregulates FOXA2 expression through transcription factor GLI2 binding to the FOXA2 promoter. Subsequently, FOXA2 maintains albumin expression in the hepatocytes lacking HNF4α and C/EBPα. In patients with massive hepatocyte loss, the expression of albumin is activated in liver progenitor cells. Albumin transcription in these cells is regulated by HNF4α or FOXA2. Taken together, HNF4α, C/EBPα and FOXA2 form a hierarchical regulatory network that ensures stable albumin expression even in pathophysiological conditions.
2022-04-06 | GSE181201 | GEO
Project description:Podocytes form filtration barrier through foot process around glomerualar basement membrane and selectively permit permeability of molecular smaller than albumin. Diabetes can cause podocyte pathological changes leading to high urine albumin level. Diabetic mouse model OVE26 has extremly high urine albumin and previously studies indicated its podocyte damaged. Here we try to find the key genes change in OVE26 diabetic mouse model podocyte by microarray assay while normal FVB mouse podocyte set as control.
2012-03-02 | GSE36209 | GEO
Project description:The goal of this experiment was to distinguish those genes regulated following acute HNF4alpha depletion compared to a developmental knockout model where gene compensation may comfound results. Expression profile of livers from 8 week old male Hnf4alpha Flox mice that express either albumin cre or the tamoxifen inducible ErT2-albumin cre for liver-specific deletion. Mice were fed a control diet or tamoxifen diet in the case of the ErT2-albumin cre to induce recombination.
2012-02-21 | GSE34581 | GEO
Project description:BACKGROUND AND AIMS: The effects of intravenous albumin on lymphocyte perturbations and defective neutrophil anti-microbial functions that characterize patients with acute-on-chronic liver failure (ACLF) are unknown. METHODS: Forty-nine patients admitted for severe acutely decompensated cirrhosis without ACLF were investigated with the use of whole-blood RNA sequencing (RNA-seq) on admission and after a median period of 15 days once they had developed ACLF. Such patients were selected because they follow a steady systemic inflammation course. Thirty patients had received albumin during the progression to ACLF but not the 19 others. Single-cell RNA-seq (scRNA-seq) in peripheral blood mononuclear cells (PBMCs) exposed ex vivo to albumin or vehicle for 2 hours, and assessment of the anti-microbial capacity of neutrophils exposed ex vivo to albumin were performed in additional patients with acutely decompensated cirrhosis. RESULTS: Analysis of whole-blood RNA-seq data revealed that patients who had received albumin exhibited specific upregulation of signatures related to B cells, plasma cells and immunoglobulins; CD4 T cells; myeloid cells; mismatch repair, cell cycle and mitosis; and transcription factors such as c-Myc and E2F family members. The use of scRNA-seq to analyze patients' PBMCs exposed ex vivo to albumin showed increases in signatures related to B cells, myeloid cells, and CD4 T cells. Neutrophils exposed ex vivo to albumin exhibited increased chemotactic and degranulation responses, enhanced phagocytosis, and increased pathogen-destroying swarming functions. CONCLUSIONS: In patients with severe acutely decompensated cirrhosis, albumin rewires transcription in B cells, CD4 T cells and mononuclear myeloid cells, and resets neutrophil anti-microbial functions to normal.
2025-04-08 | GSE171741 | GEO
Project description:Insults to the cerebral cortex, such as trauma, ischemia or infections, may result in the development of epilepsy, one of the most common neurological disorders. Previous studies have suggested that perturbations in neurovascular integrity and breakdown of the blood-brain barrier (BBB) lead to neuronal hypersynchronization and epileptiform activity, but the underlying mechanisms are unknown. As with BBB opening, treatment with albumin or with TGF-β1 results in the development of hypersynchronized epileptiform activity. Given the latent period before the appearance of epileptiform activity, we hypothesized the underlying mechanism is a transcriptional response which would be similar for BBB breakdown and exposure to albumin or TGF-β1. In search of a common pathway and transcriptional activation pattern we performed a genome wide analysis. Genomic expression analyses demonstrated similar expression patterns for BBB opening, albumin and TGF-β1 exposure. Most importantly, TGF-β pathway blockers suppressed most albumin-induced transcriptional changes.
2009-07-15 | GSE12304 | GEO
Project description:To identify genes whose expression is under the strict dependence of hepatocyte PPARa activity, we used a mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to their liver WT littermates (albumin-Cre-/- Pparaflox/flox or LWT) fed ad libitum or fasted for 24 hours.
2017-12-16 | GSE96559 | GEO
Project description:Changes in mouse liver mRNA profiles following intraperitoneal cytokine injection. Either interferon-gamma-/-, albumin-cre(-) Socs3(w/fl) mice, or albumin-cre(+) Socs3(-/fl) mice were injected with either phosphate-buffered saline, interferon-gamma, or interfeukin-6, and livers taken after 4h. Keywords = Socs3, interferon gamma, interleukin-6, il6, liver, suppressor of cytokine signalling 3 Keywords: repeat sample
2003-04-10 | GSE369 | GEO
Project description:Pparα hepatocyte-specific knockout (Pparαhep-/-) mice were generated at INRAE’s rodent facility (Toulouse, France) by mating the floxed-Pparα mouse strain with C57BL/6J albumin-Cre transgenic mice to obtain albumin-Cre+/-Pparαflox/flox mice (LKO). Albumin-Cre-/-Pparαflox/flox (Pparαhep+/+) littermates were used as controls (LWT). Twelve week-old mice were transferred in a ventilated cabinet at the specific temperature of 30°C (thermoneutrality) 2 weeks before experiments. Mice were fed ad libitum or fasted at ZT0 and given beta3 adrenergic receptor agonist: CL316243 ((3 mg/kg body weight; Sigma Aldrich) = Beta3) or vehicle (0.5% carboxymethyl cellulose in sterilized water)=vehicle) by gavage at ZT10 and sacrificed at ZT16.
2022-09-15 | GSE165558 | GEO
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to evaluate the effects of liver-specific E4BP4 overexpression under mouse albumin promoter on the liver glucose and lipid metabolism.
2024-03-31 | GSE183079 | GEO