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American Journal of Physiology. Gastrointestinal and Liver Physiology

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https://www.readbyqxmd.com/read/28104587/pkc%C3%AE-expanding-role-in-hepatic-adaptation-of-cholesterol-homeostasis-to-dietary-fat-cholesterol
#1
Devina Mehta, Kamal D Mehta
Cholesterol homeostasis relies on an intricate network of cellular processes whose deregulation in response to Western type high-fat/cholesterol diets can lead to several life-threatening pathologies. Significant advances have been made in resolving the molecular identity and regulatory function of transcription factors sensitive to fat, cholesterol, or bile acids, but whether body senses the presence of both fat and cholesterol simultaneously is not known. Assessing the impact of a high-fat/cholesterol load, rather than an individual component alone, on cholesterol homeostasis is more physiologically relevant because Western diets deliver both fat and cholesterol at the same time...
January 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28104586/synergy-of-glucagon-like-peptide-2-and-epidermal-growth-factor-co-administration-on-intestinal-adaptation-in-neonatal-piglets-with-short-bowel-syndrome
#2
David W Lim, Crystal L Levesque, Donna F Vine, Mitsuru Muto, Jacob R Koepke, Patrick N Nation, Pamela R Wizzard, Julang Li, David L Bigam, Patricia L Brubaker, Justine M Turner, Paul W Wales
BACKGROUND: Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) treatment enhance intestinal adaptation. To determine whether these growth factors exert synergistic effects on intestinal growth and function, GLP-2 and EGF-containing media (EGF-cm) were administered, alone and in combination, in neonatal piglet with short bowel syndrome (SBS). METHODS: Neonatal Landrace/Large White piglets were block-randomized to 75% mid-intestinal (JI group) or distal-intestinal (JC group) resection or sham control, with 7-d infusion of saline (control), intravenous human GLP-2 (11 nmol/kg/day) alone, enteral EGF-cm (80 μg/kg/day) alone, or GLP-2 and EGF-cm in combination...
January 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28104585/rcad-bip-pathway-is-necessary-for-the-proper-synthesis-of-digestive-enzymes-and-the-secretory-function-of-the-exocrine-pancreas
#3
Camille Miller, Yafei Cai, Tadd Patton, Sarai Graves, Honglin Li, Maria Eugenia Sabbatini
Alcoholism causes an imbalance of endoplasmic reticulum (ER) homeostasis in pancreatic acini. In those cells, the ER is involved in the synthesis and folding of pancreatic enzymes. Ufm1 (Ubiquitin-fold modifier 1) is part of a novel ubiquitin-like modification system involved in maintaining ER homeostasis. Among the components of the Ufm1 system, Regulator of C53 and DDRGK1 (RCAD) has recently been identified as an Ufm1-specific E3 ligase that promotes ufmylation of DDRGK1, a RCAD-interacting protein. We determined the importance of RCAD in the proper synthesis and secretion of pancreatic enzymes using RCAD-deficient mice...
January 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28082286/enteric-glia-cells-are-critical-to-limiting-the-intestinal-inflammatory-response-after-injury
#4
Simone Langness, Mitsuaki Kojima, Raul Coimbra, Brian P Eliceiri, Todd W Costantini
Vagal nerve stimulation (VNS) has been shown to limit intestinal inflammation following injury, however, direct connection between vagal terminals and resident intestinal immune cells have yet to be identified. We have previously shown that enteric glia cell (EGC) expression is increased after injury through a vagal-mediated pathway to help restore gut barrier function. We hypothesize that EGCs modulate immune cell recruitment following injury and relay vagal anti-inflammatory signals to resident immune cells in the gut...
January 12, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28082285/plasticity-of-neuroeffector-transmission-during-bowel-inflammation
#5
Alan E Lomax, Sabindra Pradhananga, Paul Page Bertrand
Altered gastrointestinal (GI) function contributes to the debilitating symptoms of inflammatory bowel diseases (IBD). Nerve circuits contained within the gut wall and outside of the gut play important roles in modulating motility, mucosal fluid transport and blood flow. The structure and function of these neuronal populations change during IBD. Superimposed on this plasticity is a diminished responsiveness of effector cells - smooth muscle cells, enterocytes and vascular endothelial cells - to neurotransmitters...
January 12, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28082284/hepatocyte-specific-ppara-expression-exclusively-promotes-agonist-induced-cell-proliferation-without-influence-from-non-parenchymal-cells
#6
Chad N Brocker, Jiang Yue, Donghwan Kim, Aijuan Qu, Jessica A Bonzo, Frank J Gonzalez
Peroxisome proliferator-activated receptor alpha (PPARA) is a nuclear transcription factor and key mediator of systemic lipid metabolism. Prolonged activation in rodents causes hepatocyte proliferation and hepatocellular carcinoma. Little is known about the contribution of non-parenchymal cells (NPCs) to PPARA-mediated cell proliferation. NPC contribution to PPARA agonist-induced hepatomegaly was assessed in hepatocyte (Ppara(∆Hep))- and macrophage (Ppara(∆Mac))-specific Ppara null mice. Mice were treated with the agonist Wy-14643 for 14 days and response of conditional null mice was compared to conventional knockout mice (Ppara(-/-))...
January 12, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28057611/wnt-5a-regulates-tgf%C3%AE-related-activities-in-liver-fibrosis
#7
Leonie Beljaars, Sara Daliri, Christa Dijkhuizen, Klaas Poelstra, Reinoud Gosens
WNT-5A is a secreted growth factor that belongs to the non-canonical members of the Wingless-related MMTV-integration family. Previous studies pointed to a connection between WNT-5A and the fibrogenic factor TGF-β warranting further studies into the functional role of WNT-5A in liver fibrosis. Therefore, we studied WNT-5A expressions in mouse and human fibrotic livers and examined the relation between WNT-5A and various fibrosis-associated growth factors, cytokines and extracellular matrix proteins. WNT-5A gene and protein expressions were significantly increased in fibrotic mouse and human livers compared to healthy...
January 5, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28039160/%C3%A2-potential-roles-of-enteric-glia-in-bridging-neuro-immune-communication-in-the-gut
#8
Aaron K Chow, Brian David Gulbransen
The enteric nervous system (ENS) is a network of neurons and glia that controls ongoing gastrointestinal (GI) functions. Damage or injury to the ENS can lead to functional GI disorders. Current data support the conclusion that many functional GI disorders are caused by an imbalance between gut microbes and the immune system but how the ENS is involved in these interactions is less understood. Due to the proximity of the ENS to bacteria and other foreign antigens present in the GI tract, it is important to prevent the passage of these antigens through the GI epithelium...
December 30, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28039159/gut-microbiota-differs-between-children-with-inflammatory-bowel-disease-and-healthy-siblings-in-taxonomic-and-functional-composition-a-metagenomic-analysis
#9
Rebecca Luise Knoll, Kristoffer Forslund, Jens Roat Kultima, Claudius U Meyer, Ulrike Kullmer, Shinichi Sunagawa, Peer Bork, Stephan Gehring
Current treatment for pediatric IBD patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A Case-Control (Sibling) Study was conducted analyzing fecal samples of six children with Crohn's Disease (CD), six children with Ulcerative Colitis (UC) and 12 healthy siblings by metagenomic sequencing...
December 30, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28039158/inhibition-of-sphingosine-1-phosphate-signaling-ameliorates-murine-nonalcoholic-steatohepatitis
#10
Amy S Mauer, Petra Hirsova, Jessica L Maiers, Vijay H Shah, Harmeet Malhi
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a lipotoxic disorder, wherein proinflammatory lipids, such as ceramide and its derivative sphingosine 1-phosphate (S1P), contribute to macrophage-associated liver inflammation. For example, we have previously demonstrated a role for S1P in steatotic hepatocyte-derived S1P enriched extracellular vesicles in macrophage chemotaxis in vitro. Therefore, we hypothesized that FTY720, an S1P antagonist, would ameliorate NASH by inhibiting proinflammatory monocyte chemotaxis...
December 30, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28039157/extracellular-vesicles-in-liver-diseases
#11
Sayantan Maji, Akiko Matsuda, Irene K Yan, Mansi Parasramka, Tushar Patel
Extracellular vesicles (EVs) are membrane-bound vesicles that are released by cells into their extracellular environment, have selective enrichment of specific proteins and RNA, and can mediate inter-cellular communication. In this review we highlight recent observations of the role of EVs in liver injury, viral hepatitis, alcoholic or non-alcoholic liver disease, biliary tract disease and liver cancers. Potential applications as markers of diseases or for therapeutic applications are outlined to emphasize the new opportunities that are arising from the study of EVs...
December 30, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28007748/emerging-studies-of-human-visceral-nociceptors
#12
David E Reed, Stephen J Vanner
Animal studies have led to significant advances in our understanding of pain mechanisms in the intestine that could lead to altered signaling in disorders such as irritable bowel syndrome. However, how these translate to the human afferent nervous system is unclear. Recent studies have demonstrated that it is possible to use a variety of techniques, including electrophysiological recordings, to begin to examine these concepts in humans. This mini-review examines these studies to explore how well animal studies translate to humans suffering from irritable bowel syndrome, highlight some of the advantages and technical limitations of these approaches, and to identify some priorities for future studies using human tissues...
December 22, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27979828/conditional-genetic-deletion-of-ano1-in-interstitial-cells-of-cajal-impairs-ca2-transients-and-slow-waves-in-adult-mouse-small-intestine
#13
John Malysz, Simon J Gibbons, Siva A Saravanaperumal, Peng Du, Seth T Eisenman, Chike Cao, Uhtaek Oh, Dieter Saur, Sabine Klein, Tamas Ordog, Gianrico Farrugia
Myenteric plexus interstitial cells of Cajal (ICC-MY) in the small intestine are Kit(+) electrical pacemakers that express the Ano1/TMEM16A Ca(2+)-activated Cl(-) channel, whose functions in the GI tract remain incompletely understood. In this study, an inducible Cre-LoxP-based approach was used to advance the understanding of Ano1 in ICC-MY of adult mouse small intestine. Kit(CreERT2/+);Ano1(Fl/Fl) mice were treated with tamoxifen or vehicle, and small intestines (mucosa-free) examined. Quantitative RT-PCR demonstrated ~50% reduction in Ano1 mRNA in intestines of conditional knock-outs (cKOs) compared to vehicle-treated controls...
December 15, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27979827/protective-roles-of-hepatic-gaba-signaling-in-acute-liver-injury-of-rats
#14
Shuanglian Wang, Yun-Yan Xiang, Jianchun Zhu, Fan Yi, Jingxin Li, Chuanyong Liu, Wei-Yang Lu
Gamma-aminobutyric acid (GABA) is produced by various cells through the catalytic activity of glutamic acid decarboxylase (GAD). Activation of type-A GABA receptor (GABAAR) inhibits stem cell proliferation but protects differentiated cells from injures. The present study investigated hepatic GABA signaling system and the role of this system in liver physiology and pathophysiology. RT-PCR and immunoblot assays identified GAD and GABAAR subunits in rat livers and in HepG2 and Clone 9 hepatocytes. Patch-clamp recording detected GABA-induced currents in Clone 9 hepatocytes and depolarization in WITT cholangiocytes...
December 15, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27979826/mir-200b-inhibits-tnf%C3%AE-induced-il-8-secretion-and-tight-junction-disruption-of-intestinal-epithelial-cells-in-vitro
#15
Yujie Shen, Min Zhou, Junkai Yan, Zizhen Gong, Yongtao Xiao, Cong Zhang, Peng Du, Yingwei Chen
Inflammatory bowel diseases (IBDs) are chronic, inflammatory disorders of the gastrointestinal tract with unclear aetiologies. Intestinal epithelial cells (IECs), containing crypt and villus enterocytes, occupy a critical position in the pathogenesis of IBDs and are a major producer of immunoregulatory cytokines and a key component of the intact epithelial barrier. Previously, we have reported that miR-200b is involved in the progression of IBDs and might maintain the integrity of the intestinal epithelial barrier via reducing the loss of enterocytes...
December 15, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27979825/the-critical-role-of-microbiota-within-cecal-crypts-on-the-regenerative-capacity-of-the-intestinal-epithelium-following-surgical-stress
#16
Alexander Zaborin, Monika Krezalek, Sanjiv Hyoju, Jennifer R DeFazio, Namrata Setia, Natalia Belogortseva, Vytautas P Bindokas, Qiti Guo, Olga Zaborina, John C Alverdy
Cecal crypts represent a unique niche that are normally occupied by the commensal microbiota. Due to their density and close proximity to stem cells, microbiota within cecal crypts may modulate epithelial regeneration. Here it is demonstrated that surgical stress, a process that invariably involves a short period of starvation, antibiotic exposure and tissue injury, results in cecal crypt evacuation of their microbiota. Crypts devoid of their microbiota display pathophysiological features characterized by abnormal stem cell activation as judged by Lgr5 staining, abnormal stem cell distribution with cells migrating toward the tips of the crypts, and an increase in TUNEL positive cells...
December 15, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27932503/computational-modelling-of-epithelial-fluid-and-ion-transport-in-the-parotid-duct-after-transfection-of-human-aquaporin-1
#17
Shelley Fong, John A Chiorini, James Sneyd, Vinod Suresh
Previous studies have shown that localized delivery of the aquaporin-1 (AQP1) gene to the parotid duct can restore saliva flow in minipigs following irradiation-induced salivary hypofunction. The resulting flow rate and electrochemisty of secreted saliva contradicts current understanding of ductal fluid transport. We hypothesized that changes in expression of ion transport proteins have occurred following AQP1 transfection. We use a mathematical model of ion and fluid transport across the parotid duct epithelial cells to predict the expression profile of ion transporters that are consistent with the experimental measurements of saliva composition and secretion rates...
December 8, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27932502/ca2-calmodulin-mlck-pathway-initiates-and-rhoa-rock-maintains-the-internal-anal-sphincter-smooth-muscle-tone
#18
Satish Rattan
N/A.
December 8, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27932501/molecular-mechanism-s-involved-in-differential-expression-of-vitamin-c-transporters-along-the-intestinal-tract
#19
Veedamali S Subramanian, Padmanabhan Srinivasan, Alexis J Wildman, Jonathan S Marchant, Hamid M Said
Mammalian cells utilize two transporters for the uptake of ascorbic acid (AA), the sodium-dependent vitamin C transporter-1 & -2 (SVCT-1 and SVCT-2). In the intestine, these transporters are involved in the absorption of AA and are expressed at the apical and basolateral membrane domains of the polarized epithelia, respectively. Little is known about the differential expression of these two transporters along the anterior-posterior axis of the intestinal tract and the molecular mechanism(s) that dictate this pattern of expression...
December 8, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27932500/notch1-and-notch2-regulate-epithelial-cell-proliferation-in-mouse-and-human-gastric-corpus
#20
Elise S Demitrack, Gail B Gifford, Theresa M Keeley, Nobukatsu Horita, Andrea Todisco, D Kim Turgeon, Christian W Siebel, Linda C Samuelson
The Notch signaling pathway is known to regulate stem cells and epithelial cell homeostasis in gastrointestinal tissues; however, Notch function in the corpus region of the stomach is poorly understood. In this study we examined the consequences of Notch inhibition and activation on cellular proliferation and differentiation and defined the specific Notch receptors functioning in the mouse and human corpus. Notch pathway activity was observed in the mouse corpus epithelium, and gene expression analysis revealed NOTCH1 and NOTCH2 to be the predominant Notch receptors in both mouse and human...
December 8, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
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