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Gene Expression | Page 2

Arlin B Rogers
Inbred mice are the most popular animals used for in vivo liver research. These mice are genetically defined, readily available, less expensive to maintain than larger animals, and enjoy a broad array of commercial reagents for scientific characterization. C57BL/6 mice are the most commonly used strain. However, other strains discussed including BALB/c, C3H, A/J, and FVB/N may be better suited to a particular disease model or line of investigation. Understanding the phenotypes of different inbred mouse strains facilitates informed decision-making during experimental design...
August 9, 2018: Gene Expression
Ashwani K Singal, Shannon M Bailey
Alcohol associated liver disease (AALD) is the third most common preventable cause for disease burden and mortality in the US. AALD including alcoholic hepatitis (AH) contributes to half of admissions from decompensated liver disease and 20% of all liver transplants in the US. Peripheral blood cells contribute to systemic inflammation, oxidative stress, mitochondrial dysfunction, and fibrosis in AALD and AH. Alcohol dysregulates function of lymphocytes, neutrophils, monocytes, and tissue macrophages of the innate immune system...
July 25, 2018: Gene Expression
Yogeshwar Sharma, Jinghua Liu, Kathleen E Kristian, Antonia Follenzi, Sanjeev Gupta
Background: In Wilson's disease, ATP7B mutations impair copper excretion with liver or brain damage. Healthy transplanted hepatocytes repopulate liver, excrete copper and reverse hepatic damage in animal models of Wilson's disease. In Fah-/- mice with tyrosinemia and alpha-1 antitrypsin mutant mice, liver disease is resolved by expansions of healthy hepatocytes derived from transplanted healthy bone marrow stem cells. This potential of stem cells has not been defined for Wilson's disease. Methods: In diseased Atp7b-/- mice we reconstituted bone marrow with donor cells expressing green fluorescent protein reporter from healthy transgenic mice...
July 20, 2018: Gene Expression
Scott M Thompson, Danielle E Jondal, Kim A Butters, Bruce E Knudsen, Jill L Anderson, Lewis R Roberts, Matthew R Callstrom, David A Woodrum
Purpose: To test the hypothesis that heat stress and hepatic thermal ablation induce nerve growth factor inducible (VGF) and to determine intrahepatic versus systemic VGF expression induced by thermal ablation in vivo and in patients. Materials and Methods: Hepatocytes and HCC cells were subjected to moderate(45°C) or physiologic(37°C) heat stress for 10 minutes and assessed for VGF expression at 0-72 hours post-heat stress(N≥3 experiments). Orthotopic N1S1 HCC bearing rats were randomized to sham or laser-thermal ablation (3 wattsx90s) and liver/serum were harvested at 0-7 days postablation for analysis of VGF expression(N≥6 per group)...
July 4, 2018: Gene Expression
Edward Hurley, Valerie Zabala, Joan M Boylan, Philip A Gruppuso, Jennifer A Sanders
During the immediate postnatal period, the liver, with its role in energy metabolism and macromolecule synthesis, playsa central role in the perinatal transition. Using RNA microarrays and several complementary computational analyses, we characterized changes in hepatic gene expression in the rat across a developmental period starting with the late gestation fetus (embryonic day 21), and including 30 min postnatal (PN), 4 hr PN, 12 hr PN, 1 day PN and 1 week after birth. Following subtle changes in gene expression at the earliest postnatal time point, there were marked changes that occurred between 4 hr and 12 hr after birth...
June 21, 2018: Gene Expression
Prachi Borude, Bharat Bhushan, Udayan Apte
Acetaminophen (APAP) overdose is the leading cause of acute liver failure (ALF) with limited treatment options. It is known that liver regeneration following APAP-induced ALF is a deciding factor in the final outcome. Previous studies from our laboratory using an incremental dose model involving a regenerating (300 mg/kg, APAP300) and a nonregenerating (600 mg/kg, APAP600) dose of APAP in mice have revealed several proregenerative pathways that regulate regeneration after APAP overdose. Here we report that DNA damage and repair mechanisms regulate initiation of liver regeneration following APAP overdose...
May 18, 2018: Gene Expression
Chang Yu, Xuefeng Wang, Lifeng Huang, Ying Tong, Lili Chen, Hailong Wu, Qiang Xia, Xiaoni Kong
Accumulation of mitochondrial DNA (mtDNA) mutations has been proposed to contribute to the initiation and progression of tumors. By using high-throughput sequencing strategies, we measured 33 specimens including 11 hepatocellular carcinoma (HCC) tissues, 11 corresponding adjacent tissues, and 11 normal liver tissues. We identified 194 single nucleotide variants (SNVs; including insert and deletion) in 33 liver tissues, and 13 somatic novel mutations were detected, including 7 mutations in the coding region...
May 18, 2018: Gene Expression
Na Zhan, Adeola Adebayo Michael, Kaiyuan Wu, Gang Zeng, Aaron Bell, Junyan Tao, Satdarshan P Monga
Simultaneous mutations in CTNNB1 and activation of c-MET occur in 9%-12.5% of patients with hepatocellular carcinoma (HCC). Coexpression of c-MET-V5 and mutant β-catenin-Myc in mouse liver by sleeping beauty transposon/transposase and hydrodynamic tail vein injection (SB-HTVI) led to the development of HCC with 70% molecular identity to the clinical subset. Using this model, we investigated the effect of EMD1214063, a highly selective c-MET inhibitor. Five weeks after SB-HTVI when tumors were established, EMD1214063 (10 mg/kg) was administered by gastric gavage as a single agent on 5-day-on/3-day-off schedule, compared to vehicle only control...
May 18, 2018: Gene Expression
John Y L Chiang, Jessica M Ferrell
Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism...
May 18, 2018: Gene Expression
Dirk J van der Windt, Vikas Sud, Hongji Zhang, Allan Tsung, Hai Huang
The increasing prevalence of obesity has made nonalcoholic fatty liver disease (NAFLD) the most common chronic liver disease. As a consequence, NAFLD and especially its inflammatory form nonalcoholic steatohepatitis (NASH) are the fastest increasing etiology of end-stage liver disease and hepatocellular carcinoma. Physical inactivity is related to the severity of fatty liver disease irrespective of body weight, supporting the hypothesis that increasing physical activity through exercise can improve fatty liver disease...
May 18, 2018: Gene Expression
Min You, Zhou Zhou, Michael Daniels, Alvin Jogasuria
Alcoholic liver disease (ALD) is the most prevalent form of liver disease, encompassing a spectrum of progressive pathological changes from steatosis to steatohepatitis to fibrosis/cirrhosis and hepatocellular carcinoma. Alcoholic steatosis/steatohepatitis is the initial stage of ALD and a major risk factor for advanced liver injuries. Adiponectin is a hormone secreted from adipocytes. Fibroblast growth factor (FGF) 15 (human homolog, FGF19) is an ileum-derived hormone. Adipocyte-derived adiponectin and gut-derived FGF15/19 regulate each other, share common signaling cascades, and exert similar beneficial functions...
May 18, 2018: Gene Expression
Danhui Sun, Mingjia Dai, Shanshan Shen, Chunyang Li, Xuebing Yan
The first NS3/4A hepatitis C virus (HCV) protease inhibitors telaprevir and boceprevir were approved in 2011, and both NS5A and NS5B polymerase inhibitors were launched. Recently, direct-acting antivirals (DAAs) have had a major impact on patients infected with HCV. HCV DAAs are highly effective antivirals with fewer side effects. DAAs have been developed for the treatment of HCV infection in combination with PEG-IFN-α/RBV as well as in IFN-free regimens. However, some drug resistance mutations occur when a single oral DAA is used for treatment, which indicates that there is a low-frequency drug resistance mutation in HCV patients before the application of antiviral drugs...
March 21, 2018: Gene Expression
Mboya Doffou, George Adams, William C Bowen, Shirish Paranjpe, Harish S Parihar, Huy Nguyen, George K Michalopoulos, Vishakha S Bhave
Hepatocyte to biliary transdifferentiation has been documented in various models of bile duct injury. In this process, mature hepatocytes transform into mature biliary epithelial cells by acquiring biliary phenotypic markers. Several signaling pathways including PI3 kinase, Notch, Hes1, Sox9, and Hippo are shown to be involved in the process. However, whether Oct4 is involved in hepatocyte to biliary transdifferentiation is unknown. We investigated the role of Oct4 in hepatocyte to biliary transdifferentiation utilizing an in vitro organoid culture system as a model of transdifferentiation...
March 21, 2018: Gene Expression
Kristen Stephenson, Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Joanne Thomson, Gianfranco Alpini, Heather Francis
Nonalcoholic fatty liver disease (NAFLD) is a disease of increasing interest, as its prevalence is on the rise. NAFLD has been linked to metabolic syndrome, which is becoming more common due to the Western diet. Because NAFLD can lead to cirrhosis and related complications including hepatocellular carcinoma, the increasing prevalence is concerning, and medical therapy aimed at treating NAFLD is of great interest. Researchers studying the effects of medical therapy on NAFLD use dietary mouse models. The two main types of mouse model diets are the methionine- and choline-deficient (MCD) diet and the Western-like diet (WD)...
March 21, 2018: Gene Expression
Simone Brivio, Massimiliano Cadamuro, Luca Fabris, Mario Strazzabosco
The acquisition of invasive functions by tumor cells is a first and crucial step toward the development of metastasis, which nowadays represents the main cause of cancer-related death. Cholangiocarcinoma (CCA), a primary liver cancer originating from the biliary epithelium, typically develops intrahepatic or lymph node metastases at early stages, thus preventing the majority of patients from undergoing curative treatments, consistent with their very poor prognosis. As in most carcinomas, CCA cells gradually adopt a motile, mesenchymal-like phenotype, enabling them to cross the basement membrane, detach from the primary tumor, and invade the surrounding stroma...
March 21, 2018: Gene Expression
Anup Ramachandran, Hartmut Jaeschke
Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the US, and decades of intense study of its pathogenesis resulted in the development of the antidote N-acetylcysteine, which facilitates scavenging of the reactive metabolite and is the only treatment in clinical use. However, the narrow therapeutic window of this intervention necessitates a better understanding of the intricacies of APAP-induced liver injury for the development of additional therapeutic approaches that can benefit late-presenting patients...
March 21, 2018: Gene Expression
Jonathan A Dranoff
Coffee is acknowledged as the most widely used drug worldwide. Coffee is also a foodstuff, so its use is often used to satisfy dietary urges. When used as a drug, coffee is normally consumed as a stimulant rather than to treat or prevent particular diseases. Recently, coffee consumption has been inversely related to progression of liver fibrosis to cirrhosis and even hepatocellular carcinoma. Experiments in cellular and animal models have provided biological plausibility for coffee as an antifibrotic agent in the liver...
March 21, 2018: Gene Expression
Lu Jiang, Lina Sun, Genea Edwards, Michael Manley, Darren P Wallace, Seth Septer, Chirag Manohar, Michele T Pritchard, Udayan Apte
Autosomal recessive polycystic kidney disease/congenital hepatic fibrosis (ARPKD/CHF) is a rare but fatal genetic disease characterized by progressive cyst development in the kidneys and liver. Liver cysts arise from aberrantly proliferative cholangiocytes accompanied by pericystic fibrosis and inflammation. Yes-associated protein (YAP), the downstream effector of the Hippo signaling pathway, is implicated in human hepatic malignancies such as hepatocellular carcinoma, cholangiocarcinoma, and hepatoblastoma, but its role in hepatic cystogenesis in ARPKD/CHF is unknown...
November 27, 2017: Gene Expression
Elise G Lavoie, Michel Fausther, Jessica R Goree, Jonathan A Dranoff
Epithelial response to injury is critical to the pathogenesis of biliary cirrhosis, and IL-6 has been suggested as a mediator of this phenomenon. Several liver cell types can secrete IL-6 following activation by various signaling molecules including circulating adenosine. The aims of this study were to assess whether adenosine can induce IL-6 secretion by cholangiocytes via the A2b adenosine receptor (A2bAR) and to determine the effect of A2bAR-sensitive IL-6 release on injury response in biliary cirrhosis...
November 27, 2017: Gene Expression
Takanori Konishi, Alex B Lentsch
Hepatic ischemia/reperfusion (I/R) injury is a major complication of liver surgery, including liver resection, liver transplantation, and trauma surgery. Much has been learned about the inflammatory injury response induced by I/R, including the cascade of proinflammatory mediators and recruitment of activated leukocytes. In this review, we discuss the complex network of events that culminate in liver injury after I/R, including cellular, protein, and molecular mechanisms. In addition, we address the known endogenous regulatory mediators that function to maintain homeostasis and resolve injury...
November 27, 2017: Gene Expression
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