A5053605944- MicroRNA in disease regulation
- Liver Disease Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Liver physiology and pathology
- Liver Disease and Transplantation
- Macrophage Migration Inhibitory Factor
- Kruppel-like factors research
- Galectins and Cancer Biology
- Adenosine and Purinergic Signaling
- Alcohol Consumption and Health Effects
- Phagocytosis and Immune Regulation
- Pluripotent Stem Cells Research
- Cholinesterase and Neurodegenerative Diseases
- Diabetes and associated disorders
- Ion channel regulation and function
- Endoplasmic Reticulum Stress and Disease
- Heparin-Induced Thrombocytopenia and Thrombosis
- Chemical synthesis and alkaloids
- Organ Transplantation Techniques and Outcomes
- SARS-CoV-2 and COVID-19 Research
- Pancreatic function and diabetes
- COVID-19 Clinical Research Studies
- Advanced Glycation End Products research
- Diet, Metabolism, and Disease
- Epigenetics and DNA Methylation
University of California Davis Medical Center
2009-2024
University of California, Davis
2011-2023
Icahn School of Medicine at Mount Sinai
2023
University of Southern California
2012
University of California, San Francisco
2012
University of Pennsylvania
2012
University of Hong Kong
2002-2004
Hong Kong University of Science and Technology
2002-2004
Hepatic stellate cell activation is a main feature of liver fibrogenesis. We have previously shown that phagocytosis apoptotic bodies by cells induces procollagen α1 (I) and transforming growth factor beta (TGF-β) expression in vitro . Here we further investigated the downstream effects studying NADPH oxidase its link to TGF-β1 an immortalized human line several models fibrosis. Phagocytosis LX-1 significantly increased superoxide production both extracellular intracellular milieus. By...
Activation of hepatic stellate cells (HSC) results in their proliferation and the secretion extracellular matrix (ECM) proteins, which leads to fibrosis. microRNAs (miRNAs) have been shown regulate various cell functions, such as proliferation, differentiation, apoptosis. Hence, we analyzed miRNAs that were differentially expressed HSC isolated from sham-operated bile duct-ligated rats. Expression two miRNAs, miRNA-150 miRNA-194, was reduced fibrotic rats compared with animals. These...
Hepatic methionine metabolism may play an essential role in regulating methylation status and liver injury Wilson's disease (WD) through the inhibition of S-adenosylhomocysteine hydrolase (SAHH) by copper (Cu) consequent accumulation (SAH). We studied transcript levels selected genes related to injury, SAHH, SAH, DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b), global tx-j mouse (tx-j), animal model WD. Findings were compared those control C3H mice, response Cu chelation penicillamine (PCA)...
Hepatic stellate cells (HSC), the key fibrogenic of liver, transdifferentiate into myofibroblasts upon phagocytosis apoptotic hepatocytes. Galectin-3, a β-galactoside-binding lectin, is regulator phagocytic process. In this study, our aim was to study mechanism by which extracellular galectin-3 modulates HSC and activation. The role in engulfment evaluated integrin binding assays primary HSC. Galectin-3 expression studied real-time PCR enzyme-linked immunosorbent assay, vivo studies were...
Macrophage activation is an important feature of primary biliary cholangitis (PBC) pathogenesis and other cholestatic liver diseases. Galectin-3 (Gal3), a pleiotropic lectin, produced by monocytic cells macrophages. However, its role in PBC has not been addressed. We hypothesized that Gal3 key to induce NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome macrophages turn propagate proinflammatory IL-17 signaling. In tissues from patients with dnTGF-βRII mice, model...
Oxidative stress is a common feature observed in wide spectrum of chronic liver diseases including viral hepatitis, alcoholic, and nonalcoholic steatohepatitis. The nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are emerging as major sources reactive oxygen species (ROS). Several isoforms expressed the liver, NOX1, NOX2, NOX4. While phagocytic NOX2 has been known to play an important role Kupffer cell neutrophil activity inflammation, nonphagocytic NOX homologues...
The self-renewal capacity ascribed to hESCs is paralleled in cancer cell proliferation, suggesting that a common network of genes may facilitate the promotion these traits. However, molecular mechanisms are involved regulating silencing as stem cells differentiate into quiescent cellular lineages remain poorly understood. Here, we show differentiated specific miR-122 exemplifies this regulatory attribute by suppressing translation gene, Pkm2, which commonly enriched and liver (HCCs),...
Type 2 diabetes is clinically associated with progressive necroinflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Advanced glycation end-products (AGEs) accumulate during prolonged hyperglycemia, but the mechanistic pathways that lead to accelerated liver have not been well defined. In this study, we show AGEs clearance receptor AGER1 was downregulated patients NASH our models, whereas proinflammatory RAGE induced. These findings were necroinflammatory, fibrogenic, pro-oxidant...
The expression of acetylcholinesterase (AChE) is markedly increased during myogenic differentiation C2C12 myoblasts to myotubes; the mediated by intrinsic factor(s) muscle differentiation. In order analyze molecular mechanisms regulating AChE differentiation, a ∼2.2-kb human promoter tagged with luciferase reporter gene, namely pAChE-Luc, was stably transfected into cells. profile promoter-driven activity myotubes found be similar that endogenous catalytic subunit. increase reciprocally...
Advanced glycation endproducts (AGEs) accumulate in patients with diabetes, yet the link between AGEs and inflammatory fibrogenic activity nonalcoholic steatohepatitis (NASH) has not been explored. Tumor necrosis factor alpha (TNF-α)-converting enzyme (TACE) is at center of processes. Because main natural regulator TACE tissue inhibitor metalloproteinase 3 (Timp3), we hypothesized that induce through nicotinamide adenine dinucleotide phosphate reduced oxidase 2 (NOX2); down-regulation...
The cardiac glycoside digoxin was identified as a potent suppressor of pyruvate kinase isoform 2-hypoxia-inducible factor-α (PKM2-HIF-1α) pathway activation in liver injury mouse models via intraperitoneal injection. We have assessed the therapeutic effects to reduce nonalcoholic steatohepatitis (NASH) by clinically relevant oral route mice and analyzed cellular basis for this effect with differential involvement cell subsets. C57BL/6J male were placed on high-fat diet (HFD) 10 wk started...
At the vertebrate neuromuscular junction (nmj), ATP is known to be coreleased with acetylcholine from synaptic vesicles. We have previously shown that P2Y<sub>1</sub> receptor localized at nmj. Here, we extend findings show another nucleotide receptor, P2Y<sub>2</sub>, also there and jointly mediates trophic responses ATP. The P2Y<sub>2</sub> mRNA in rat muscle increased during development peaked adulthood. protein was become restricted nmjs embryonic development, chick rat. In both...
Presynaptic motor neuron synthesizes and secretes acetylcholinesterase (AChE) at vertebrate neuromuscular junctions. In order to determine the retrograde role of muscle in regulating expression AChE neuron, a chimeric co-culture NG108-15 cell, cholinergic cell line that resembles with chick myotube was established mimic contact vitro. A DNA construct human promoter tagged luciferase (pAChE-Luc) stably transfected into cells. The myotubes robustly stimulated activity as well endogenous...
The adipocyte hormone, leptin has been demonstrated to have profibrogenic actions in vitro and animal models. However, no correlation was found between plasma levels fibrosis stage humans. Thus, our aim study whether soluble receptor (SLR) or free index (FLI; calculated as the ratio of SLR), may correlate better with features metabolic syndrome histological grade nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). We studied a population (n = 104) morbidly obese...
The self-renewal capacity ascribed to embryonic stem cells (ESC) is reminiscent of cancer cell proliferation, raising speculation that a common network genes may regulate these traits. A search for general regulators traits yielded set microRNAs which expression highly enriched in human ESCs and liver (HCC) but attenuated differentiated quiescent hepatocytes. Here, we show promote hESC self-renewal, as well HCC when overexpressed normally hepatocytes, induce proliferation activate signaling...
Abstract Recruitment of inflammatory cells is a major feature alcoholic liver injury however; the signals and cellular sources regulating this are not well defined. C-C chemokine receptor type 2 (CCR2) expressed by active hepatic stellate (HSC) key monocyte recruitment signal. Activated HSC also important hydrogen peroxide resulting from activation NADPH oxidase 4 (NOX4). As role NOX in early has been addressed, we studied NOX4-mediated regulation CCR2/CCL2 mRNA stability. NOX4 was...
The presence of a collagenous protein (ColQ) characterizes the collagen-tailed forms acetylcholinesterase and butyrylcholinesterase at vertebrate neuromuscular junctions which is tethered in synaptic basal lamina. ColQ subunits, differing mostly by their signal sequences, are encoded transcripts ColQ-1 ColQ-1a, differentially expressed slow fast twitch muscles mammals. Two distinct promoters, pColQ-1 pColQ-1a, were isolated from upstream sequences human COLQ gene; they showed muscle-specific...
Background and Aims Older patients with obesity/type II diabetes mellitus frequently present advanced NASH. Whether this is due to specific molecular pathways that accelerate fibrosis during aging unknown. Activation of the Src homology 2 domain–containing collagen‐related (Shc) proteins redox stress have been recognized in aging; however, their link NASH has not explored. Approach Results Shc expression increased livers older NASH, as assessed by real time quantitative PCR (RT‐qPCR) or...