Cellular and Molecular Gastroenterology and Hepatology

Editor picks for Cellular and Molecular Gastroenterology and Hepatology

Porcine Esophageal Submucosal Gland Culture Model Shows Capacity for Proliferation and Differentiation We describe a novel porcine 3-dimensional culture model that reproduces esophageal submucosal gland proliferation in vivo associated with cancer and injury.
Oct. 22, 2017

Analysis of Hepatitis C Virus Particle Heterogeneity in Immunodeficient Human Liver Chimeric fah-/- Mice Our work indicates that the heterogeneity in buoyant density of infectious HCV particles evolves over the course of infection and can be influenced by diet.
Oct. 22, 2017

Hepatitis B Virus Activates Signal Transducer and Activator of Transcription 3 Supporting Hepatocyte Survival and Virus Replication HBV activates STAT3 signaling in hepatocytes to foster its own replication but also to prevent apoptosis of infected cells.
Oct. 22, 2017

Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in Humans This study provides the first demonstration of S Typhi–specific responses in the human terminal ileum mucosa .
Oct. 22, 2017

Hepatocyte-Specific Deletion of Mouse Lamin A/C Leads to Male-Selective Steatohepatitis Lamin A/C absence leads to male-selective fatty liver disease and predisposes to nonalcoholic steatohepatitis and fibrosis.
Oct. 22, 2017

Setting up a Lab: The Early Years Dr Habtezion provides advice on successfully navigating the early years of an independent career as a physician-scientist.
Oct. 22, 2017

The Farnesoid X Receptor: Good for BAD Herein, we review current concepts of bile acid diarrhea pathogenesis and the potential role for the farnesoid X receptor in its treatment.
Oct. 22, 2017

Maintaining a Vibrant and Productive Laboratory as a Senior Investigator Dr Boyer discusses his decision to maintain a research program at this stage of his career.
Sept. 1, 2017

Bacterial Autophagy: Offense and Defense at the Host–Pathogen Interface Here we discuss some of these mechanisms, with a special emphasis on the enteric pathogen Salmonella enterica serovar Typhimurium.
Sept. 1, 2017

Do Animal Models of Acute Pancreatitis Reproduce Human Disease? Multiple animal models of clinical pancreatitis have been developed, however, limitations with respect to the pathobiology of human disease make it difficult to assess the validity of animal models.
Sept. 1, 2017

Cellular and Molecular Gastroenterology and Hepatology RSS

  • Mutant KRAS Exosomes Influence the Metabolic State of the Colon Microenvironment

    KRAS is mutated in approximately 30% to 40% of colorectal cancers (CRC) and KRAS mutations lead to an adaptive metabolic shift in cancer cells with increased aerobic glycolysis (Warburg effect) in part owing to higher uptake of glucose. In mutant KRAS CRC cells, overexpression of the glucose transporter GLUT-1 (SLC2A1) is observed and contributes to increased glucose uptake, leading to acquisition of this metabolic change. However, the ability of KRAS to reach beyond the cancer cell and alter the metabolic state within the tumor microenvironment is not entirely clear.
  • Host-gut microbiota crosstalk in intestinal adaptation

    Intestinal adaptation is a multifactorial compensatory process which occurs in the remaining bowel of intestinal failure patients after small bowel loss or damage. This review provides an overview of the current knowledge on host-microbiota interactions and their potential ability to modulate the intestinal adaptive response.
  • Esophageal Adenocarcinomas: A Need for Speed Driven by Immune Pathways That Have Druggable Targets

    Despite advances in multimodality therapy and the development of agents that target tumor growthpromoting pathways, the 5-year survival of patients with esophageal adenocarcinoma (EAC) remains less than 20%. Most of these targeted agents have been directed at growth factor receptor tyrosine kinases, with clinical trials yielding woefully disappointing results. Genomic studies of EACs have shown amplification of multiple receptor tyrosine kinases and their downstream signaling pathways, showing a complex, diffuse, and redundant spider web of signaling networks that might elude inhibition even by combinations of several molecularly targeted agents.
  • Parietal Cell Death by Cytokines

    Parietal cell atrophy in the human stomach occurs along a continuum of gastric inflammation, atrophy, and then metaplasia, a preneoplastic lesion. In mice, and to a lesser extent in human beings, the best-characterized typeof metaplasia is spasmolytic polypeptide-expressing metaplasia. Inflammation in the stomach generally arises in response to autoimmune gastritis or an infection from Helicobacter pylori. Although relatively rare, autoimmune gastritis is known to occur in response to autoantibodies to parietal cell proteins, specifically the and subunits of the proton pump H+, K+-adenosine triphosphatase.
  • Proteomic Study Defines How Alcohol Alters ER Structure and Redox Proteome to Trigger ER Stress and Acinar Cell Pathology in Pancreatitis

    In a new study published in this issue of Cellular andMolecular Gastroenterology and Hepatology, Waldron etal1 used proteomic approaches to define how ethanol modifies the redox state of the pancreas ER proteome. These structural changes and ER dysfunction may contribute to ethanol-induced pathology associated with pancreatitis.
  • Estrogen-Mediated Effects Underlie Gender Bias in Inflammatory Bowel Disease

    The gastrointestinal tract is continuously exposed toa myriad of food antigens and symbiotic microflora, thus modulation of the inflammatory response is tightly regulated to prevent aberrant immune activation andchronic inflammation. However, in individuals with a genetic and environmental predisposition (eg, altered microbiota, viral or bacterial infection, chemical additives, or pollutants), regulation of intestinal inflammation is impaired. This condition leads to a chronic relapsing immune activation against luminal antigens, also known as inflammatory bowel disease (IBD).
  • Move Over Caco-2 Cells: Human-Induced Organoids Meet Gut-on-a-Chip

    The intestinal epithelium serves as both a crucial barrier and a critical site of interaction between the body and the environment. As such, it comprises a large surface area, and is implicated in a wide range of diseases including inflammatory bowel disease, celiac disease, infectious diarrheas, and intestinal cancers. Architecturally, the small intestine is notable for its proliferative crypts, where stem and transit-amplifying progenitor cells reside, and villi, which consist of multiple differentiated cell types from the absorptive and secretory lineages, including enterocytes, goblet cells, Paneth cells, tuft cells, M cells, and enteroendocrine cells.
  • Single-cell computational strategies for lineage reconstruction in tissue systems

    Recent developments in single-cell technologies have stimulated growth in analysis techniques, in particular, computational tools for ordering cell states as a function of pseudotemporal progression. We provide a review of current algorithms and a generalized single-cell workflow tailored for trajectory analysis, with a focus on underlying assumptions and caveats.
  • OST-OST Guards the Ileal Enterocyte From the Accumulation of Toxic Levels of Bile Acids

    OST-OST (SLC51A and SLC51B) is a heteromeric organic solute transporter that was first isolated from the liver of a marine skate, Leukoraja erinacia, by Ballatori etal in a quest for a sodium-independent transporter of hepatic bile acid uptake.1 Subsequent studies identified SLC51A and B orthologues from mice and human beings. These 2 gene products are the only known members of this SLC family and are unique in requiring 2 subunits for function. Human SLC51A encodes for a 340amino acid protein with 7 membrane-spanning domains whereas SLC51B encodes for a 128amino acid single-membrane-spanning domain protein.
  • Molecular Basis and Differentiation-Associated Alterations of Anion Secretion in Human Duodenal Enteroid Monolayers

    Human enteroids present a novel toolto study human intestinal ion transport physiology and pathophysiology. The present study describes the contributions of Cl- and HCO3- secretion to total cyclic adenosine monophosphate (cAMP)-stimulated electrogenic anion secretion in human duodenal enteroid monolayers and the relevant changes after differentiation.
  • Cysteine protease-mediated autocleavage of Clostridium difficile toxins regulates their proinflammatory activity

    This study identified an unexpected function of C. difficile toxin autoprocessing that regulates in vivo inflammatory activities of TcdA and TcdB. The differential autoprocessing mediated by the cysteine proteases of the two toxins regulates their major bioactivities.
  • Mesenteric adipose-derived stromal cells from Crohns Disease patients induce protective effects in colonic epithelial cells and mice with colitis

    Extracellular mediators from mesenteric adipose-derived stromal cells (ADSCs) promote colonocyte proliferation and the resolution of inflammation in a disease-dependent manner. ADSC-derived mediators such as lactoferrin may provide therapeutic potential to promote remission from intestinal inflammation in Crohns disease patients.
  • Human Fetal-Derived Enterospheres Provide Insights on Intestinal Development and a Novel Model to Study Necrotizing Enterocolitis (NEC)

    Untreated necrotizing enterocolitis (NEC) can lead to massive inflammation resulting in intestinal necrosis with a high mortality rate in preterm infants. Limited access to human samples and relevant experimental models have hampered progress in NEC pathogenesis. Earlier evidence has suggested that bacterial colonization of an immature and developing intestine can lead to an abnormally high inflammatory response to bacterial bioproducts. The aim of our study was to use human fetal organoids to gain insights into NEC pathogenesis.
  • Esophageal 3D Culture Systems as Modeling Tools in Esophageal Epithelial Pathobiology and Personalized Medicine

    The stratified squamous epithelium of the esophagus shows a proliferative basal layer of keratinocytes that undergo terminal differentiation in overlying suprabasal layers. Esophageal pathologies, including eosinophilic esophagitis, gastroesophageal reflux disease, Barrett's esophagus, squamous cell carcinoma, and adenocarcinoma, cause perturbations in the esophageal epithelial proliferation-differentiation gradient. Three-dimensional (3D) culture platforms mimicking invivo esophageal epithelial tissue architecture exvivo have emerged as powerful experimental tools for the investigation of esophageal biology in the context of homeostasis and pathology.
  • Obesity and Binge Drinking: Two Hits Driving Liver Fibrosis Progression?

    Alcoholic fatty liver disease and nonalcoholic fatty liver disease frequently are associated with alcohol consumption and obesity. Both diseases start with steatosis/steatohepatitis, and some patients can develop advanced liver injuries and subsequent permanent liver damage, including fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. Epidemiologic evidence has shown that drinking alcohol synergistically increases the prevalence and severity of liver injury in obese individuals. Likewise, liver damage in alcohol abusers is greatly exacerbated by obesity.
  • A Sabbatical: The Gift That Keeps on Giving

    Scott Friedman is the Dean for Therapeutic Discovery and Chief of the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai, a former president of the American Association for the Study of Liver Diseases, and a leader in liver fibrosis research. He speaks often of the transformative role his sabbatical played in his career, and this month encourages other researchers to consider similar academic experiences, providing advice on what to doand not doto make a sabbatical worthwhile.
  • CFTR and the Regulation of Crypt Cell Proliferation

    Gastrointestinal manifestations of cystic fibrosis (CF) may be quite severe and a cause of significant morbidity. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) result in meconium ileus, and, in later life, small-bowel bacterial overgrowth, bowel obstructions, and an increased incidence of intestinal cancers. A 2013 study of more than 40,000 patients from 250 US CF centers showed an increased risk of colon cancer (standardized incidence ratio, 6.2) and small-bowel cancer (standardized incidence ratio, 11.5).
  • siRNA Library Screening Identifies a Druggable Immune-Signature Driving Esophageal Adenocarcinoma Cell Growth

    Effective therapeutic approaches are urgently required to tackle the alarmingly poor survival outcomes in esophageal adenocarcinoma (EAC) patients. EAC originates from within the intestinal-type metaplasia, Barretts esophagus, a condition arising on a background of gastroesophageal reflux disease and associated inflammation.
  • Mutant KRAS Exosomes Alter the Metabolic State ofRecipient Colonic Epithelial Cells

    In colorectal cancer (CRC) cells, mutant KRAS cell-autonomously imparts Warburg-like1 metabolic changes through induction of GLUT-1 (SLC2A1).2,3 We previously reported that mutant KRAS has marked effects on the constituents of CRC exosomes, including proteins and enzymes involved in metabolism and glycolysis.4,5 The present studies were designed to test whether mutant KRAS exosomes can alter the metabolic state cell-nonautonomously in recipient colonic epithelial cells.
  • Regulation of Gastric Lgr5+ve Cell Homeostasis by Bone Morphogenetic Protein (BMP) Signaling and Inflammatory Stimuli

    Gastric Lgr5 cells exert important functions during injury and homeostasis. Bone morphogenetic protein (BMP) signaling regulates gastric inflammation and epithelial homeostasis. We investigated if BMP signaling controls the fate of Lgr5+ve cells during inflammation.
  • NAFLD Phenotype in Patients With V-ATPase Proton Pump Assembly Defects

    Nonalcoholic fatty liver disease (NAFLD) is a very common chronic liver disease marked by hepatic fat accumulation. This might trigger inflammation and liver cell injury, a condition known as nonalcoholic steatohepatitis. Nonalcoholic steatohepatitis may promote fibrogenesis and evolve toward cirrhosis and hepatocellular carcinoma, and is considered the phenotypic extension of NAFLD.
  • Bioengineered Systems and Designer Matrices That Recapitulate the Intestinal Stem Cell Niche

    The relationship between intestinal stem cells (ISCs) and the surrounding niche environment is complex and dynamic. Key factors localized at the base of the crypt are necessary to promote ISC self-renewal and proliferation, to ultimately provide a constant stream of differentiated cells to maintain the epithelial barrier. These factors diminish as epithelial cells divide, migrate away from the crypt base, differentiate into the postmitotic lineages, and end their life span in approximately 7 days when they are sloughed into the intestinal lumen.
  • Organic Solute Transporter - Protects Ileal Enterocytes From Bile AcidInduced Injury

    Ileal bile acid absorption is mediated by uptake via the apical sodium-dependent bile acid transporter (ASBT), and export via the basolateral heteromeric organic solute transporter - (OST-OST). In this study, we investigated the cytotoxic effects of enterocyte bile acid stasis in Ost-/- mice, including the temporal relationship between intestinal injury and initiation of the enterohepatic circulation of bile acids.
  • NRF2 Induction for NASH Treatment: A New Hope Rises

    Nonalcoholic fatty liver disease (NAFLD) is a complex disease characterized by excessive fat storage in the liver. NAFLD ranges from simple steatosis (fat accumulation) to nonalcoholic steatohepatitis (NASH), which in addition to steatosis involves liver inflammation (hepatitis) and fibrosis, and can progress into cirrhosis or liver cancer. Coupled with a worldwide increase in obesity, type 2 diabetes, metabolic syndrome, and hypertension, the incidence of NAFLD/NASH is also steadily increasing.
  • Ethanol Induced Disordering of Pancreatic Acinar Cell Endoplasmic Reticulum: An ER Stress/Defective Unfolded Protein Response Model

    Heavy alcohol drinking is associated with pancreatitis, whereas moderate intake lowers the risk.Mice fed ethanol long term show no pancreas damage unlessadaptive/protective responses mediating proteostasis are disrupted. Pancreatic acini synthesize digestive enzymes (largely serine hydrolases) in the endoplasmic reticulum (ER), where perturbations (eg, alcohol consumption) activate adaptive unfolded protein responses orchestrated by spliced X-box binding protein 1 (XBP1). Here, we examined ethanol-induced early structural changes in pancreatic ERproteins.
  • Stinging Tight Junctions With WASPs

    Extracellular bacterial pathogens can hijack the N-WASPbased machinery to promote actin nucleation and polymerization in their hosts. One well-studied example is the family of attaching and effacing (A/E) bacterial pathogens, which includes the human diarrheagenic enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E coli, and the mouse pathogen Citrobacter rodentium. These bacteria, which infect the intestinal epithelium, activate a syringe-like machinery, termed the type III secretion system, through which they translocate a battery of protein effectors from their own cytoplasm into the infected host.
  • Interleukin 17A Promotes Parietal Cell Atrophy by Inducing Apoptosis

    Atrophic gastritis caused by chronic inflammation in the gastric mucosa leads to the loss of gastric glandular cells, including acid-secreting parietal cells. Parietal cell atrophy in a setting of chronic inflammation induces spasmolytic polypeptide expressing metaplasia, a critical step in gastric carcinogenesis. However, the mechanisms by which inflammation causes parietal cell atrophy and spasmolytic polypeptide expressing metaplasia are not well defined. We investigated the role of interleukin 17A (IL17A) in causing parietal cell atrophy.
  • Enhanced Utilization of Induced Pluripotent Stem CellDerived Human Intestinal Organoids Using Microengineered Chips

    Human intestinal organoids derived from induced pluripotent stem cells have tremendous potential to elucidate the intestinal epitheliums role inhealth and disease, but it is difficult to directly assay thesecomplex structures. This study sought to make this technology more amenable for study by obtaining epithelial cells from induced pluripotent stem cellderived human intestinal organoids and incorporating them into small microengineered Chips. We then investigated if these cells within the Chip were polarized, had the 4 major intestinal epithelial subtypes, and were biologically responsive to exogenous stimuli.
  • State of the Journal: CMGHs Progress, Prospects, and Impact Factor

    Cellular and Molecular Gastroenterology and Hepatology (CMGH) was established to create a forum for high-quality, mechanistic studies of the gastrointestinal tract, liver, and pancreas. CMGH has now completed its third full year of publication and has developed a reputation as a rigorous and highly regarded platform for basic and translational research. CMGH has also become known for a prompt, fair, and transparent review process in which authors are treated with respect and have access to editors.
  • Estrogen Receptor Loss-of-Function Protects Female Mice From DSS-Induced Experimental Colitis

    Males are at greater risk than femalesfor developing ulcerative colitis (UC) and experiencing worse clinical disease13; the molecular basis for this sex bias remains unclear. An important regulatory mechanism of colonic homeostasis is via noncanonical estrogen receptor (ER) signaling. Very low levels of circulating estrogen are required to bind transmembrane and cytosolic ERs, such that immune responses in both sexes are subject toregulation by estrogen. Estrogen receptor (ER) is expressed abundantly in the human colon,4,5 where it has a critical role in maintaining barrier function and colonic architecture.
  • Antibiotic Treatment Leads to Fecal Escherichia coli and Coliphage Expansion in Severely Malnourished Diarrhea Patients

    Malnutrition predisposes to diarrhea and diarrhea adversely affects the nutritional status creating a vicious cycle.1 The role of the gut microbiome in malnutrition is an active research area.2 Parenteral antibiotics are recommended by the World Health Organization in hospitalized pediatric patients with severe acute malnutrition (SAM) presenting signs of infections.3 Stool microbiota data for such patients are, however, lacking. To fill this gap, we studied the stool microbiota in 19 SAM patients from Bangladesh hospitalized with acute diarrhea (AD) and compared it with that of matched 20 healthy control subjects (HC) (Supplementary Table1).
  • Microfabricated Crypt Scaffolds: A New Foundation forEvaluating Human Colon Stem Cells

    The emergence of 3-dimensional organoid technology has significantly advanced the understanding of epithelial stem cell biology within the past decade. Stem cells of the gastrointestinal tract have served as a template for this technology, with initial propagation of mouse intestinal enteroids and colonoids (derived from adult smallintestine or colon crypt units, respectively) and subsequent adaptation of these protocols for human tissue.14 As such, researchers may now evaluate basic intestinal and/or colonic stem cell properties directly from patient tissue.
  • Jumonji: Welcome to the World of Interferon Signaling in Alcohol and HCV

    Alcoholic liver disease and hepatitis C virus (HCV) infection, either alone or in combination, affect 2 out of 3 persons living with chronic liver disease in the Western world. Alcohol consumption not only increases the risk of HCV infection, but also works synergistically with HCV to increase hepatotoxicity and the progression to hepatocellular carcinoma (HCC).1 It is known that the increase in hepatotoxicity is caused in part by increased viral replication and impaired innate immune responses.
  • GEMMs Are a Gem When it Comes to Defining the Role of HIF2 in Mucinous Cystic Neoplasms

    The most frequently diagnosed pancreatic malignancy is pancreatic ductal adenocarcinoma (PDA). Invasive PDA constitutes nearly 85% of pancreatic neoplasms, with a strong majority of the patients presenting with distal metastasis at the time of diagnosis, differentiating PDA as one of the most lethal cancers with a 5-year survival rate near 5%. Invasive PDA is dependent on a preceding proliferative and inflammatory pancreatitis events, most frequently pancreatic intraepithelial neoplasms (PanIN) formation with the less frequently observed precursor oncogenic event, mucinous cystic neoplasms (MCN).
  • Bioengineered Liver Models for Drug Testing and Cell Differentiation Studies

    Invitro models of the human liver are important for the following: (1) mitigating the risk of drug-induced liver injury to human beings, (2) modeling human liver diseases, (3) elucidating the role of single and combinatorial microenvironmental cues on liver cell function, and(4) enabling cell-based therapies in the clinic. Methods to isolate and culture primary human hepatocytes (PHHs), the gold standard for building human livermodels, were developed several decades ago; however, PHHs show a precipitous decline in phenotypic functions in 2-dimensional extracellular matrixcoated conventional culture formats, which does not allow chronic treatment with drugs and other stimuli.
  • Taming the Wild West of Organoids, Enteroids, and Mini-Guts

    The complex nature of an organ, made up of multiple tissue and cells types, poses an incredible challenge to biologists wishing to interrogate homeostasis or disease. Because of this complexity, it often is difficult to ascertain the cause-and-effect relationship of an experimental manipulation in these systems. For example, in the intestine, a perturbation to the epithelium may elicit an immune response; however, it is difficult to determine if this response is a direct result of the epithelial perturbation, or a consequence of a secondary effect, such as translocation of bacteria across the epithelium.
  • Formation of Giant Lysosome in Neonatal Ileal Enterocytes Requires Endotubin

    Enterocyte maturation involves the development of a highly sophisticated brush border, tight junctions, and an intracellular membrane network pivotal for the intestinal barrier and absorptive functions. Genetic or environmental factors that disrupt the enterocytes proper development can severely impact growth and survival. Interestingly, the developing enterocytes in the ileum of neonates have a transient but distinct morphologic feature: the presence of giant lysosomes in the subapical cytoplasmic region.
  • Epigenetic Reprogramming of Human Hepatoma Cells: A Low-Cost Option for Drug Metabolism Assessment

    Primary cultures of hepatocytes are widely considered the gold standard for evaluating the hepatic metabolism of pharmacologic molecules.1 However, limited access to human hepatocytes has led to the development of various alternative models.25 The procedures used to generate these cells remain complex and time-consuming. In addition, the resulting hepatocytes frequently display heterogeneous hepatic gene expression, rapidly dedifferentiate, and lose their metabolic functions, which are essential for biological, pharmacologic, and toxicologic studies.
  • Engineered Livers for Infectious Diseases

    Engineered liver systems come in a variety of platform models, from 2-dimensional cocultures of primary humanhepatocytes and stem cellderived progeny, to 3-dimensional organoids and humanized mice. Because of the species-specificity of many human hepatropic pathogens, these engineered systems have been essential tools for biologic discovery and therapeutic agent development in the context of liver-dependent infectious diseases. Although improvement of existing models is always beneficial, and the addition of a robust immune component is a particular need, at present, considerable progress has been made using this combination of research platforms.
  • The Endosomal Protein Endotubin Is Required for EnterocyteDifferentiation

    During late embryonic development and through weaning, enterocytes of the ileum are highly endocytic. Defects in endocytosis and trafficking are implicated in neonatal disease, however, the mechanisms regulating trafficking during the developmental period are incompletely understood. The apical endosomal protein endotubin (EDTB) is highly expressed in the late embryonic and neonatal ileum. In epithelial cells invitro, EDTB regulates both trafficking of tight junction proteins and proliferation through modulation of YAP activity.
  • Pancreatic HIF2 Stabilization Leads to Chronic Pancreatitis and Predisposes to Mucinous Cystic Neoplasm

    Tissue hypoxia controls cell differentiation in the embryonic pancreas, and promotes tumor growth in pancreatic cancer. The cellular response to hypoxia is controlled by the hypoxia-inducible factor (HIF) proteins, including HIF2. Previous studies of HIF action in the pancreas have relied on loss-of-function mouse models, and the effects of HIF2 expression in the pancreas have remained undefined.
  • Formation of Human Colonic Crypt Array by Application of Chemical Gradients Across a Shaped Epithelial Monolayer

    The successful culture of intestinal organoids has greatly enhanced our understanding of intestinal stem cell physiology and enabled the generation of novel intestinal disease models. Although of tremendous value, intestinal organoid culture systems have not yet fully recapitulated the anatomy or physiology of the invivo intestinal epithelium. The aim of this work was to re-create an intestinal epithelium with a high density of polarized crypts that respond in a physiologic manner to addition of growth factors, metabolites, or cytokines to the basal or luminal tissue surface as occurs invivo.
  • Demethylase JMJD6 as a New Regulator of Interferon Signaling: Effects of HCV and Ethanol Metabolism

    Alcohol-induced progression of hepatitis C virus (HCV) infection is related to dysfunction of innate immunity in hepatocytes. Endogenously produced interferon (IFN) induces activation of interferon-stimulated genes (ISGs) via triggering of the Janus kinasesignal transducer and activator of transcription 1 (STAT1) pathway. This activation requires protein methyltransferase 1regulated arginine methylation of STAT1. Here, we aimed to study whether STAT1 methylation also depended on the levels of demethylase jumonji domain-containing 6 protein (JMJD6) and whether ethanol and HCV affect JMJD6 expression in hepatocytes.
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