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Cellular and Molecular Gastroenterology and Hepatology

Eitaro Aihara, Andrea L Matthis, Rebekah A Karns, Kristen A Engevik, Peihua Jiang, Jiang Wang, Bruce R Yacyshyn, Marshall H Montrose
BACKGROUND & AIMS: The peptic ulcer heals through a complex process, although the ulcer relapse often occurs several years later after healing. Our hypothesis is that even after visual evidence of healing of gastric ulceration, the regenerated epithelium is aberrant for an extended interval, increasing susceptibility of the regenerated epithelium to damage and further diseases. METHODS: Gastric ulcers were induced in mice by serosal topical application of acetic acid...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
Spencer G Willet, Jason C Mills
Gastric diseases cause considerable worldwide burden. However, the stomach is still poorly understood in terms of the molecular-cellular processes that govern its development and homeostasis. In particular, the complex relationship between the differentiated cell types located within the stomach and the stem and progenitor cells that give rise to them is significantly understudied relative to other organs. In this review, we will highlight the current state of the literature relating to specification of gastric cell lineages from embryogenesis to adulthood...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
Brad W Warner
After massive small-bowel resection, the remnant bowel compensates by a process termed adaptation. Adaptation is characterized by villus elongation and crypt deepening, which increases the capacity for absorption and digestion per unit length. The mechanisms/mediators of this important response are multiple. The purpose of this review is to highlight the major basic contributions in elucidating a more comprehensive understanding of this process.
July 2016: Cellular and Molecular Gastroenterology and Hepatology
Michael Camilleri, David R Linden
Accurately measuring the complex motor behaviors of the gastrointestinal tract has tremendous value for the understanding, diagnosis and treatment of digestive diseases. This review synthesizes the literature regarding current tests that are used in both humans and animals. There remains further opportunity to enhance such tests, especially when such tests are able to provide value in both the preclinical and the clinical settings.
July 2016: Cellular and Molecular Gastroenterology and Hepatology
Johanna Louhimo, Michael L Steer, George Perides
BACKGROUND AND AIMS: Severe acute pancreatitis is characterized by acinar cell death and inflammation. Necroptosis is an aggressive and pro-inflammatory mode of cell death that can be prevented by necrostatin-1 administration or RIP3 deletion. METHODS: Mouse pancreatic acinar cells were incubated with supramaximally stimulating concentrations of caerulein or sub-micellar concentrations of TLCS and necroptosis was inhibited by either addition of necrostatin or by RIP3 deletion...
July 2016: Cellular and Molecular Gastroenterology and Hepatology
Vishal Singh, Beng San Yeoh, Benoit Chassaing, Benyue Zhang, Piu Saha, Xia Xiao, Deepika Awasthi, Rangaiah Shashidharamurthy, Madhu Dikshit, Andrew Gewirtz, Matam Vijay-Kumar
BACKGROUND & AIMS: Lipocalin 2 (Lcn2) is a multifunctional innate immune protein whose expression closely correlates with extent of intestinal inflammation. However, whether Lcn2 plays a role in the pathogenesis of gut inflammation is unknown. Herein, we investigated the extent to which Lcn2 regulates inflammation and gut bacterial dysbiosis in mouse models of IBD. METHODS: Lcn2 expression was monitored in murine colitis models and upon microbiota ablation/restoration...
July 2016: Cellular and Molecular Gastroenterology and Hepatology
Duke Geem, Vu Ngo, Akihito Harusato, Benoit Chassaing, Andrew T Gewirtz, Rodney D Newberry, Timothy L Denning
: This study showed that the absence of CCR7 or mesenteric lymph nodes/gut-associated lymphoid tissue did not appreciably impact total intestinal Foxp3+ regulatory T cell representation in the steady-state. However, mesenteric lymph nodes/GALT are required for normal peripherally induced Foxp3+ regulatory T cell differentiation in the small intestine, but not in the large intestine. BACKGROUND & AIMS: Foxp3+ regulatory T cells (Tregs) in the intestine promote immune tolerance to enteric antigens...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
Emilie Viennois, Sarah A Ingersoll, Saravanan Ayyadurai, Yuan Zhao, Lixin Wang, Mingzhen Zhang, Moon Kwon Han, Pallavi Garg, Bo Xiao, Didier Merlin
BACKGROUND AND AIMS: The human intestinal peptide transporter 1, hPepT1, is expressed in the small intestine at low levels in the healthy colon and upregulated during inflammatory bowel disease. hPepT1 plays a role in mouse colitis and human studies have demonstrated that chronic intestinal inflammation leads to colorectal cancer (colitis-associated cancer; CAC). Hence, we assessed here the role of PepT1 in CAC. METHODS: Mice with hPepT1 overexpression in intestinal epithelial cells (TG) or PepT1 (PepT1-KO) deletion were used and CAC was induced by AOM/DSS...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
Mallappa Anitha, François Reichardt, Sahar Tabatabavakili, Behtash Ghazi Nezami, Benoit Chassaing, Simon Mwangi, Matam Vijay-Kumar, Andrew Gewirtz, Shanthi Srinivasan
BACKGROUND & AIMS: High-fat diet (HFD) feeding is associated with gastrointestinal motility disorders. We recently reported delayed colonic motility in mice fed a HFD mice for 11 weeks. In this study, we investigated the contributing role of gut microbiota in HFD-induced gut dysmotility. METHODS: Male C57BL/6 mice were fed a HFD (60% kcal fat) or a regular/control diet (RD) (18% kcal fat) for 13 weeks. Serum and fecal endotoxin levels were measured, and relative amounts of specific gut bacteria in the feces assessed by real time PCR...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
Onur Cil, Puay-Wah Phuan, Sujin Lee, Joseph Tan, Peter M Haggie, Marc H Levin, Liang Sun, Jay R Thiagarajah, Tonghui Ma, A S Verkman
BACKGROUND & AIMS: Constipation is a common clinical problem that negatively impacts quality of life and is associated with significant health care costs. Activation of the cystic fibrosis transmembrane regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents. We hypothesized that direct activation of CFTR would cause fluid secretion and reverse the excessive dehydration of stool found in constipation...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
Bridget M Kohlnhofer, Cayla A Thompson, Emily M Walker, Michele A Battle
BACKGROUND & AIMS: The embryonic small intestinal epithelium is highly proliferative, and although much is known about mechanisms regulating proliferation in the adult intestine, the mechanisms controlling epithelial cell proliferation in the developing intestine are less clear. GATA4, a transcription factor that regulates proliferation in other developing tissues, is first expressed early in the developing gut in midgut endoderm. GATA4 function within midgut endoderm and the early intestinal epithelium has not been investigated...
March 2016: Cellular and Molecular Gastroenterology and Hepatology
Gianluca Cipriani, Simon J Gibbons, Purna C Kashyap, Gianrico Farrugia
There is an increasing awareness of the role of macrophages in the regulation and maintenance of gastrointestinal function in health and disease. This work has proceeded in the context of an increased understanding of the complex phenotypic variation in macrophages throughout the body and has revealed previously un-identified roles for macrophages in diseases like gastroparesis, post-operative ileus and inflammatory bowel disease. Opportunities for exploiting the phenotypic modulation of tissue resident macrophages have been identified as possible therapies for some of these diseases...
March 1, 2016: Cellular and Molecular Gastroenterology and Hepatology
G Victoria Weis, Byron C Knowles, Eunyoung Choi, Anna E Goldstein, Janice A Williams, Elizabeth H Manning, Joseph T Roland, Lynne A Lapierre, James R Goldenring
BACKGROUND AND AIMS: Inactivating mutations in MYO5B cause severe neonatal diarrhea in Microvillus Inclusion Disease. Loss of active MYO5B causes the formation of pathognomonic inclusions and aberrations in brush border enzymes. METHODS: We developed three mouse models of germline, constitutively intestinal targeted and inducible intestinal targeted deletion of MYO5B. The mice were evaluated for enterocyte cellular morphology. RESULTS: Germline MYO5B KO mice showed early diarrhea and failure to thrive with evident microvillus inclusions and loss of apical transporters in the duodenum...
February 1, 2016: Cellular and Molecular Gastroenterology and Hepatology
Huiyuan Tang, Katie Partyka, Peter Hsueh, Jessica Y Sinha, Doron Kletter, Herbert Zeh, Ying Huang, Randall E Brand, Brian B Haab
BACKGROUND AND AIMS: The CA19-9 antigen is the current best biomarker for pancreatic cancer, but it is not elevated in about 25% of pancreatic cancer patients at a cutoff that gives a 25% false-positive rate. We hypothesized that antigens related to the CA19-9 antigen, which is a glycan called sialyl-Lewis A (sLeA), are elevated in distinct subsets of pancreatic cancers. METHODS: We profiled the levels of multiple glycans and mucin glycoforms in plasma from 200 subjects with either pancreatic cancer or benign pancreatic disease, and we validated selected findings in additional cohorts of 116 and 100 subjects, the latter run blinded and including cancers that exclusively were early-stage...
February 1, 2016: Cellular and Molecular Gastroenterology and Hepatology
Jinsheng Yu, M Isabel Ordiz, Jennifer Stauber, Nurmohammad Shaikh, Indi Trehan, Erica Barnell, Richard D Head, Ken Maleta, Phillip I Tarr, Mark J Manary
BACKGROUND & AIMS: Environmental enteric dysfunction (EED), a chronic diffuse inflammation of the small intestine, is associated with stunting in children in the developing world. The pathobiology of EED is poorly understood because of the lack of a method to elucidate the host response. This study tested a novel microarray method to overcome limitation of RNA sequencing to interrogate the host transcriptome in feces in Malawian children with EED. METHODS: In 259 children, EED was measured by lactulose permeability (%L)...
February 2016: Cellular and Molecular Gastroenterology and Hepatology
Reina Aoki, Michal Shoshkes-Carmel, Nan Gao, Soona Shin, Catherine L May, Maria L Golson, Adam M Zahm, Michael Ray, Caroline L Wiser, Christopher V E Wright, Klaus H Kaestner
BACKGROUND & AIMS: Intestinal epithelial stem cells that express Lgr5 and/or Bmi1 continuously replicate and generate differentiated cells throughout life(1). Previously, Paneth cells were suggested to constitute an epithelium-intrinsic niche that regulates the behavior of these stem cells(2). However, ablating Paneth cells has no effect on maintenance of functional stem cells(3-5). Here, we demonstrate definitively that a small subset of mesenchymal, subepithelial cells expressing the winged-helix transcription factor Foxl1 are a critical component of the intestinal stem cell niche...
February 1, 2016: Cellular and Molecular Gastroenterology and Hepatology
David Bernardo, Lydia Durant, Elizabeth R Mann, Elizabeth Bassity, Enrique Montalvillo, Ripple Man, Rakesh Vora, Durga Reddi, Fahri Bayiroglu, Luis Fernández-Salazar, Nick R English, Simon T C Peake, Jon Landy, Gui H Lee, George Malietzis, Yi Harn Siaw, Aravinth U Murugananthan, Phil Hendy, Eva Sánchez-Recio, Robin K S Phillips, Jose A Garrote, Paul Scott, Julian Parkhill, Malte Paulsen, Ailsa L Hart, Hafid O Al-Hassi, Eduardo Arranz, Alan W Walker, Simon R Carding, Stella C Knight
BACKGROUND & AIMS: Most knowledge about gastrointestinal (GI)-tract dendritic cells (DC) relies on murine studies where CD103(+) DC specialize in generating immune tolerance with the functionality of CD11b(+/-) subsets being unclear. Information about human GI-DC is scarce, especially regarding regional specifications. Here, we characterized human DC properties throughout the human colon. METHODS: Paired proximal (right/ascending) and distal (left/descending) human colonic biopsies from 95 healthy subjects were taken; DC were assessed by flow cytometry and microbiota composition assessed by 16S rRNA gene sequencing...
January 2016: Cellular and Molecular Gastroenterology and Hepatology
Julie In, Jennifer Foulke-Abel, Nicholas C Zachos, Anne-Marie Hansen, James B Kaper, Harris D Bernstein, Marc Halushka, Sarah Blutt, Mary K Estes, Mark Donowitz, Olga Kovbasnjuk
BACKGROUND AND AIMS: Enterohemorrhagic E. coli (EHEC) causes over 70,000 episodes of foodborne diarrhea annually in the USA. The early sequence of events which precede life-threatening hemorrhagic colitis and hemolytic uremic syndrome are not fully understood due to the initial asymptomatic phase of the disease and the lack of a suitable animal model. The aim of this study was to determine the initial molecular events in the interaction between EHEC and human colonic epithelium. METHODS: Human colonoids derived from adult proximal colonic stem cells were developed into monolayers to study EHEC-epithelial interactions...
January 1, 2016: Cellular and Molecular Gastroenterology and Hepatology
Miao Liu, Shujuan Chen, Mei-Fei Yueh, Guangji Wang, Haiping Hao, Robert H Tukey
BACKGROUND & AIMS: The UDP-glucuronosyltransferases (UGTs) are part of the cells machinery that protects the tissues from a toxicant insult by environmental and host cell metabolites. We have investigated the mechanism behind tumor growth and UGT repression. METHODS: We initially silenced the Ugt1 locus in human colon cell lines and investigated markers and responses linked to p53 activation. To examine the role of the Ugt1 locus in p53-directed apoptosis and tumorigenesis, experiments were conducted to induce acute colon inflammation and chemical induced colon cancer in mice where we have selectively deleted the Ugt1 locus in the intestinal epithelial cells (Ugt1(ΔIEC) mice)...
January 2016: Cellular and Molecular Gastroenterology and Hepatology
Isola A M Brown, Jonathon L McClain, Ralph E Watson, Bhavik A Patel, Brian D Gulbransen
BACKGROUND AND AIMS: The concept of enteric glia as regulators of intestinal homeostasis is slowly gaining acceptance as a central concept in neurogastroenterology. Yet how glia contribute to intestinal disease is still poorly understood. Purines generated during inflammation drive enteric neuron death by activating neuronal P2X7 purine receptors (P2X7R), triggering ATP release via neuronal pannexin-1 channels that subsequently recruits intracellular calcium ([Ca(2+)]i) responses in the surrounding enteric glia...
January 1, 2016: Cellular and Molecular Gastroenterology and Hepatology
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