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

  • The endosomal protein endotubin is required for enterocyte differentiation

    The apical endosomal protein endotubin is highly expressed during enterocyte development. Here we show that endotubin is required for membrane trafficking and enterocyte morphogenesis. We propose that endotubin serves as a scaffold that modulates apical membrane traffic.
  • A Molecular Signature of Murine NASH: A Step Closer to a Human Predictive Biomarker?

    Fibrosis is the single best predictor of clinical outcomes in patients with nonalcoholic steatohepatitis (NASH).1,2 Advanced fibrosis portends liver-related mortality and determines the need for liver transplantation.3 Current diagnostic tools assess the presence of hepatic fibrosis but do not predict its development in patients at risk. Risk stratification based on propensity for liver fibrosis is a key factor for the selection of patients who benefit from close follow-up evaluation and medical therapy once approved.
  • 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

    Human colonic epithelia were cultured on a microfabricated scaffold under a growth factor gradient in order to generate crypt structures. Responses to cytokines or bacterial metabolite gradients were assessed from altered stem and differentiated cell numbers and locations.
  • Advancing Intestinal Organoid Technology Toward RegenerativeMedicine

    With the emergence of technologies to culture intestinal epithelial cells invitro as various forms of intestinal organoids, there is growing interest in using such cultured intestinal cells as a source for tissue engineering and regenerative medicine. One such approach would be to combine the organoid technology with methodologies to engineer the culture environment, particularly the three-dimensional scaffold materials, to generate intestines that exquisitely recapitulate their original structures and functions.
  • Indian Hedgehog Suppresses Intestinal Inflammation

    Hedgehog signaling is an evolutionarily conserved pathway that is important for tissue patterning and repair and has been implicated in inflammatory responses for several tissues. However, the gene and cellular targets of the Hedgehog signaling pathway that orchestrate the inflammatory responses are not clearly defined. Hedgehog signaling is mediated by 3 different ligands (sonic hedgehog [Shh], Indian hedgehog [Ihh], and Desert hedgehog [Dhh]), multiple co-receptors (patched, smoothened, growth arrest-specific 1, cell adhesion molecule-related/down-regulated byoncogenes, and brother of cell adhesion molecule-related/down-regulated by oncogenes), 3 transcriptional effectors (glioma [Gli]-associated oncogene homologs 1, 2, 3), and additional regulatory factors.
  • 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.
  • Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model

    The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for hepatic fibrosis.
  • Role of Vasoactive Intestinal Peptide in Promoting the Pathogenesis of Eosinophilic Esophagitis (EoE)

    Eosinophilic esophagitis (EoE) is associated with eosinophil and mast cellaccumulation, which promotes dysphagia and esophageal dysmotility.1,2 Cytokines and chemokines implicated in eosinophil-, mast cell, and basophil-mediated EoE pathogenesis include interleukin (IL)-5, IL-13, thymicstromal lymphopoietin, and eotaxin-3.36 A correlation between IL-5 and eotaxin-3 expression and eosinophil infiltration has been observed.7 Nevertheless, it is not clear if eotaxin-3 is the only chemokine, or one of several, that directs eosinophil accumulation in EoE.
  • Hypoxia in the Gut

    A continuous supply of molecular oxygen is essential for the maintenance of oxidative metabolism and thereby the function and survival of most cells of the human body. Over the course of evolution, we have developed the capacity, at the cellular level, to counteract the threat of developing hypoxia by eliciting an early warning adaptive response that is driven primarily by a transcription factor termed the hypoxia-inducible factor (HIF). In hypoxia, HIF becomes activated and drives the expression of a cohort of genes that promote adaptation to hypoxia including primary regulators of erythropoiesis (eg, erythropoietin), angiogenesis (eg, vascular endothelial growth factor), and metabolism (eg, glycolytic enzymes).
  • Location Matters in Defining T Cellmediated Immunity in Response to Salmonella Typhi Vaccination

    Infection with Salmonella enterica serovar Typhi results in nearly 250,000 deaths and more than 21 million illnesses worldwide. S Typhi is transmitted through the fecal-oral route through contaminated food or water and therefore is a major global health problem in regions that lack the infrastructure to provide safe water and ensure adequate sanitation. Of the 2 widely used S Typhi vaccines, Ty21a is an oral live-attenuated vaccine that confers moderate protection against infection for several years.
  • Lamin Deficiency in the Liver Sets the Stage for Nonalcoholic Steatohepatitis Development in Males

    Nuclear lamins are type V intermediate filament proteins that play important roles in maintaining nuclear shape and in transcriptional regulation. Moreover, they serve as signaling scaffolds at the inner nuclear membrane.1 Nuclear lamins fall into 2 separate classes, A-type and B-type, which are encoded by distinct genes. Mutations in their genes lead to tissue-selective disease phenotypes, termed laminopathies, which can affect muscle, adipose tissue, bone, liver, or multiple tissues depending on the site of the mutation.
  • Heterogeneity of Hepatitis C Virus Particles and Their Evolution During Infection

    Hepatitis C virus (HCV) was identified by molecular cloning of its RNA genome after conventional methods of virus identification failed. This failure was dueto both low levels of HCV particles in the blood of infected patients and particle heterogeneity. HCV is a highly variable virus. In addition to 6 genotypes and more than 60 subtypes, HCV mutants circulate in the blood as millions of quasispecies, many of which are able to escape host immune responses and even direct-acting antiviral (DAA) therapy.
  • Indian Hedgehog Suppresses a Stromal CellDriven Intestinal Immune Response

    Upon intestinal epithelial damage a complex wound healing response is initiated to restore epithelial integrity and defend against pathogenic invasion. Epithelium-derived Indian Hedgehog (Ihh) functions as a critical sensor in this process. Signaling occurs in a paracrine manner because the receptor for Ihh is expressed only in the mesenchyme, but the exact Hedgehog target cell has remained elusive. The aim of this study was to elucidate further the nature of this target cell in the context of intestinal inflammation.
  • Setting up a Lab: The Early Years

    This months Paths and Places column was written by Aida Habtezion, an Associate Professor of Medicine (Gastroenterology and Hepatology) at Stanford University. Dr Habtezion, who studies leukocyte trafficking and the immune response in the gut, provides advice on successfully navigating the early years of an independent career as a physician-scientist. Dr. Habtezion has received multiple awards and was recently promoted to Associate Professor with tenure, making her an ideal role model for early career success.
  • Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in Humans

    Systemic cellular immunity elicited by the Ty21a oral typhoid vaccine has been extensively characterized. However, very limited data are available in humans regarding mucosal immunity at the site of infection (terminal ileum [TI]). Here we investigated the host immunity elicited by Ty21a immunization on terminal ileumlamina propria mononuclear cells (LPMC) and peripheral blood in volunteers undergoing routine colonoscopy.
  • Early Diagnosis of Gastroesophageal Cancers and the Cytosponge: A Work in Progress

    In the Perspective article in the March issue of Cellular and Molecular Gastroenterology and Hepatology,1 the Cytosponge erroneously was cited during the publication process as a Medtronic device (Medtronic, Minneapolis, MN). We would like to clarify that all published studies on Cytosponge to date have been performed using a research design patented by the Medical Research Council UK and made by local manufacturers and performed under permission from the Medical Health Regulatory Agency of the United Kingdom.
  • Porcine Esophageal Submucosal Gland Culture Model Shows Capacity for Proliferation and Differentiation

    Although cells comprising esophageal submucosal glands (ESMGs) represent a potential progenitor cell niche, new models are needed to understand their capacity to proliferate and differentiate. By histologic appearance, ESMGs have been associated with both overlying normal squamous epithelium and columnar epithelium. Our aim was toassess ESMG proliferation and differentiation in a 3-dimensional culture model.
  • Hepatitis B Virus Activates Signal Transducer and Activator of Transcription 3 Supporting Hepatocyte Survival and Virus Replication

    The human hepatitis B virus (HBV) is a major cause of chronic hepatitis and hepatocellular carcinoma, but molecular mechanisms driving liver disease and carcinogenesis are largely unknown. We therefore studied cellular pathways altered by HBV infection.
  • Analysis of Hepatitis C Virus Particle Heterogeneity in Immunodeficient Human Liver Chimeric fah-/- Mice

    Hepatitis C virus (HCV) is a leading cause of chronic liver diseases and the most common indication for liver transplantation in the United States. HCV particles in the blood of infected patients are characterized by heterogeneous buoyant densities, likely owing to HCV association with lipoproteins. However, clinical isolates are not infectious invitro and the relative infectivity of the particles with respect to their buoyant density therefore cannot be determined, pointing to the need for better invivo model systems.
  • Neutrophils as Components of Mucosal Homeostasis

    Inflammatory responses in the intestinal mucosa inevitably result in the recruitment of neutrophils (polymorphonuclear leukocytes [PMNs]). Epithelial cells that line the mucosa play an integral role in the recruitment, maintenance, and clearance of PMNs at sites of inflammation. The consequences of such PMNepithelial interactions often determine tissue responses and, ultimately, organ function. For this reason, there is significant interest in understanding how PMNs function in the mucosa during inflammation.
  • Hepatocyte-Specific Deletion of Mouse Lamin A/C Leads to Male-Selective Steatohepatitis

    Lamins are nuclear intermediate filament proteins that comprise the major components of the nuclear lamina. Mutations in LMNA, which encodeslamins A/C, cause laminopathies, including lipodystrophy, cardiomyopathy, and premature aging syndromes. However, the role of lamins in the liver is unknown, and itis unclear whether laminopathy-associated liver disease iscaused by primary hepatocyte defects or systemic alterations.
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