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Gene Expression

Rong Zhang, Alexander T Kikuchi, Toshimasa Nakao, Jacquelyn O Russell, Morgan E Preziosi, Minakshi Poddar, Sucha Singh, Aaron W Bell, Steven G England, Satdarshan P Monga
Background : Alterations in the Wnt signaling pathway including those impacting hepatic stellate cells (HSC) have been implicated in liver fibrosis. Methods : In the current study, we first examined the expression of Wnt genes in human HSC (HHSC) after treatment with a pro-fibrogenic factor TGFβ1. Next, we generated HSC-specific Wntless (Wls) knockout (KO) using the Lrat-cre and Wls-floxed mice. KO and littermate controls (CON) were characterized for any basal phenotype and subjected to two liver fibrosis protocols...
September 20, 2018: Gene Expression
Jie Zhao, Maura O'Neil, Anusha Vittal, Steven A Weinman, Irina Tikhanovich
Alcohol is a well-established risk factor for hepatocellular carcinoma, but the mechanisms are not well understood. Several studies suggested that alcohol promotes tumor growth by altering immune cell phenotypesin the liver.Arginine methylation is a common posttranslational modification generated mostly by a single protein,PRMT1. In myeloid cells PRMT1 is a key regulator of immune response. Myeloid specific PRMT1 knockout mice are hyper-responsive to LPS and deficient in PPARγ-dependent macrophage M2 polarization...
September 18, 2018: Gene Expression
Sirisha Achanta, Aalap Verma, Ankita Srivastava, Harshavardhan Nilakantan, Jan B Hoek, Rajanikanth Vadigepalli
The analysis of molecular states of individual cells, as defined by their mRNA expression profiles and protein composition, has gained widespread interest in studying biological phenomena ranging from embryonic development to homeostatic tissue function and genesis and evolution of cancers. Although the molecular content of individual cells in a tissue can vary widely, their molecular states tend to be constrained within a transcriptional landscape partly described by the canonical archetypes of a population of cells...
September 6, 2018: Gene Expression
Akiko Matsuda, Kaori Ishiguro, Irene K Yan, Tushar Patel
Aberrant activation of β -catenin signaling is frequently observed in hepatocellular cancer. Although Wnt/ β-catenin signaling can be targeted by Vitamin D, therapeutic use of Vitamin D for this purpose is not currently established. We evaluated the therapeutic use of Vitamin D or its analogues using a synthetic transgenic mouse of hepato-carcinogenesis induced by mutant β-catenin, and MET overexpression in which 75% of mice develop well differentiated HCC within 8 weeks in the absence of fibrosis. Vitamin D receptor expression was similar in both tumoral and non-tumoral tissue...
August 29, 2018: Gene Expression
Nandini Agarwal, Branimir Popovic, Nicole J Martucci, Nicolas A Fraunhoffer, Alejandro Soto-Gutierrez
Directed differentiation of hepatocytes from induced pluripotent stem cells (iPSCs) holds promise as source material for treating some liver disorders. The unlimited availability of perfectly differentiated iPSC-derived hepatocytes will dramatically facilitate cell therapies. While systems to manufacture large quantities of iPSCs-derived cells have been developed, we have been unable to generate and maintain stable and mature adult liver cells ex vivo. This short review highlights important challenges and possible solutions to the current state of hepatocyte biofabrication for cellular therapies to treat liver diseases...
August 24, 2018: Gene Expression
Chao Hou, Wenwen Feng, Shan Wei, Yulin Wang, Xiaoyi Xu, Jin Wei, Ziliang Ma, Yongsheng Du, Jialin Guo, Yu He, Fanyun Kong, Renxian Tang, Kuiyang Zheng
Non-alcoholic fatty liver disease (NAFLD) is a global health problem characterized with excessive accumulation of fat in the liver without effect of other pathological factors included hepatitis infection and alcohol abuse. Current studies indicate that gene factors play important roles in the development of NAFLD. However, the molecular characteristics of differentially expressed genes (DEGs) and associated mechanisms with NAFLD have not been well elucidated. Using two microarray data associated with the gene expression profiling in liver tissues of NAFLD mice models, we identified and selected several common key DEGs that contributed to NAFLD...
August 22, 2018: Gene Expression
Stephanie Grant, Matthew McMillin, Gabriel Frampton, Anca D Petrescu, Elaina Williams, Victoria Jaeger, Jessica Kain, Sharon DeMorrow
Acute liver failure is a devastating consequence of hepatotoxic liver injury that can lead to the development of hepatic encephalopathy. There is no consensus on the best model to represent these syndromes in mice, and therefore the aim of this study was to classify hepatic and neurological consequences of azoxymethane- and thioacetamide-induced liver injury. Azoxymethane-treated mice were euthanized at time points representing absence of minor and significant stages of neurological decline. Thioacetamide-treated mice had tissue collected at up to 3 days following daily injections...
August 22, 2018: Gene Expression
Yifeng Wang, David Matye, Nga Nguyen, Yuxia Zhang, Tiangang Li
Cysteine dioxygenase 1 (CDO1) converts cysteine to cysteine sulfinic acid, which can be further converted by cysteine sulfinic acid decarboxylase (CSAD) to hypotaurine for taurine production. This cysteine catabolic pathway plays a major role in regulating hepatic cysteine homeostasis. Furthermore, taurine is used for bile acid conjugation, which enhances bile acid solubility and physiological function in the gut. Recent studies show that this cysteine catabolic pathway is repressed by bile acid signaling, but the molecular mechanisms have not been fully elucidated...
August 22, 2018: Gene Expression
Mehwish Khaliq, Sungjin Ko, Yinzi Liu, Hualin Wang, Yonghua Sun, Lila Solnica-Krezel, Donghun Shin
After liver injury, regeneration manifests as either (1) hepatocytes proliferating to restore the lost hepatocyte mass or (2) if hepatocyte proliferation is compromised, biliary epithelial cells (BECs) dedifferentiating into liver progenitor cells (LPCs), which subsequently differentiate into hepatocytes. Following pharmacogenetic ablation of hepatocytes in Tg(fabp10a:CFP-NTR) zebrafish, resulting in severe liver injury, signal transducer and activator of transcription 3 (Stat3) and its target gene and negative regulator, socs3a, were upregulated in regenerating livers...
August 22, 2018: Gene Expression
Elsa Ghurburrun, Ivan Borbath, Frédéric P Lemaigre, Patrick Jacquemin
The liver and pancreas are closely associated organs that share a common embryological origin. They display amphicrine properties and have similar exocrine organization with parenchymal cells, namely, hepatocytes and acinar cells, secreting bile and pancreatic juice into the duodenum via a converging network of bile ducts and pancreatic ducts. Here we compare and highlight the similarities of molecular mechanisms leading to liver and pancreatic cancer development. We suggest that unraveling tumor development in an organ may provide insight into our understanding of carcinogenesis in the other organ...
August 22, 2018: Gene Expression
Laurent Ehrlich, April O'Brien, Chad Hall, Tori White, Lixian Chen, Nan Wu, Julie Venter, Marinda Scrushy, Muhammad Mubarak, Fanyin Meng, David Dostal, Chaodong Wu, Terry C Lairmore, Gianfranco Alpini, Shannon Glaser
α7-nAChR is a nicotinic acetylcholine receptor [specifically expressed on hepatic stellate cells (HSCs), Kupffer cells, and cholangiocytes] that regulates inflammation and apoptosis in the liver. Thus, targeting α7-nAChR may be therapeutic in biliary diseases. Bile duct ligation (BDL) was performed on wild-type (WT) and α7-nAChR-/- mice. We first evaluated the expression of α7-nAChR by immunohistochemistry (IHC) in liver sections. IHC was also performed to assess intrahepatic bile duct mass (IBDM), and Sirius Red staining was performed to quantify the amount of collagen deposition...
August 22, 2018: Gene Expression
Morgan Preziosi, Minakshi Poddar, Sucha Singh, Satdarshan P Monga
Activation of the Wnt/β-catenin signaling is reported in large subsets of hepatocellular carcinoma (HCC). Upregulation of Wnt genes is one contributing mechanism. In the current study, we sought to address the role of hepatocyte-derived Wnts in a model of hepatic injury, fibrosis, and carcinogenesis. We subjected hepatocyte-specific Wntless knockout mice (HP-KO), unable to secrete Wnts from hepatocytes, and littermate controls (HP-CON) to diethylnitrosamine and carbon tetrachloride (DEN/CCl4) and harvested at 3, 5, and 6 months for histological and molecular analysis...
August 22, 2018: Gene Expression
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
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