AJP: Gastrointestinal and Liver Physiology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

CRISPR/Cas 9 genome editing and its applications in organoids
Organoids are three-dimensional (3D) structures derived from adult or embryonic stem cells that maintain many structural and functional features of their respective organ. Recently, genome editing based on the bacterial defense mechanism CRISPR/Cas9 has emerged as an easily applicable and reliable laboratory tool. Combining organoids and CRISPR/Cas9 creates exciting new opportunities to study organ development and human disease in vitro. The potential applications of CRISPR in organoids are only beginning to be explored. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - March 9, 2017 Category: Gastroenterology Authors: Driehuis, E., Clevers, H. Tags: REVIEW Source Type: research

Gastrointestinal immune and microbiome changes during parenteral nutrition
Parenteral nutrition (PN) is a lifesaving therapy that provides intravenous nutrition support to patients who cannot, or should not, feed via the gastrointestinal (GI) tract. Unfortunately, PN also carries certain risks related to infection and metabolic complications compared with enteral nutrition. In this review, an overview of PN and GI immune and microbiome changes is provided. PN impacts the gut-associated lymphoid tissue functions, especially adaptive immune cells, changes the intestinal epithelium and chemical secretions, and significantly alters the intestinal microbiome. Collectively, these changes functionally r...
Source: AJP: Gastrointestinal and Liver Physiology - March 9, 2017 Category: Gastroenterology Authors: Pierre, J. F. Tags: REVIEW Source Type: research

Conditional genetic deletion of Ano1 in interstitial cells of Cajal impairs Ca2+ transients and slow waves in adult mouse small intestine
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. KitCreERT2/+;Ano1Fl/Fl mice were treated with tamoxifen or vehicle, and small intestines (mucosa free) were examined. Quantitative RT-PCR demonstrated ~50% reduction in Ano1 mRNA in intestines of conditional knockouts (cKOs) compared with vehicle-treated controls. Whole mount immunohistochemistry showed a mosaic/patchy pattern loss of Ano1 protein in ICC networks. Ca2+ transients in ICC-MY network of cKOs displayed reduced duration compared with highly synchronized controls and showed ...
Source: AJP: Gastrointestinal and Liver Physiology - February 28, 2017 Category: Gastroenterology Authors: Malysz, J., Gibbons, S. J., Saravanaperumal, S. A., Du, P., Eisenman, S. T., Cao, C., Oh, U., Saur, D., Klein, S., Ordog, T., Farrugia, G. Tags: RESEARCH ARTICLE Source Type: research

WNT-5A regulates TGF-{beta}-related activities in liver fibrosis
In conclusion, WNT-5A paralleled collagen I levels in fibrotic mouse and human livers. WNT-5A expression in myofibroblasts is induced by the profibrotic factor TGF-β and plays an important role in TGF-β-induced regulation of fibrotic matrix proteins, whereas its expression can be reversed upon treatment, both in vitro and in vivo. NEW & NOTEWORTHY This study describes the localization and functional role of WNT-5A in human and mouse fibrotic livers. Hepatic WNT-5A expression parallels collagen type I expression. In vivo and in vitro, the myofibroblasts were identified as the key hepatic cells producing WNT-5A...
Source: AJP: Gastrointestinal and Liver Physiology - February 28, 2017 Category: Gastroenterology Authors: Beljaars, L., Daliri, S., Dijkhuizen, C., Poelstra, K., Gosens, R. Tags: RESEARCH ARTICLE Source Type: research

Protective roles of hepatic GABA signaling in acute liver injury of rats
-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. The function of ...
Source: AJP: Gastrointestinal and Liver Physiology - February 28, 2017 Category: Gastroenterology Authors: Wang, S., Xiang, Y.-Y., Zhu, J., Yi, F., Li, J., Liu, C., Lu, W.-Y. Tags: RESEARCH ARTICLE Source Type: research

Emerging studies of human visceral nociceptors
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, highlights some of the advantages and technical limit...
Source: AJP: Gastrointestinal and Liver Physiology - February 28, 2017 Category: Gastroenterology Authors: Reed, D. E., Vanner, S. J. Tags: MINI-REVIEW Source Type: research

Extracellular vesicles in liver diseases
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 intercellular communication. In this review we highlight recent observations of the role of EVs in liver injury, viral hepatitis, alcoholic or nonalcoholic 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. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - February 28, 2017 Category: Gastroenterology Authors: Maji, S., Matsuda, A., Yan, I. K., Parasramka, M., Patel, T. Tags: MINI-REVIEW Source Type: research

Homeostasis of the gut barrier and potential biomarkers
The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota pla...
Source: AJP: Gastrointestinal and Liver Physiology - February 28, 2017 Category: Gastroenterology Authors: Wells, J. M., Brummer, R. J., Derrien, M., MacDonald, T. T., Troost, F., Cani, P. D., Theodorou, V., Dekker, J., Meheust, A., de Vos, W. M., Mercenier, A., Nauta, A., Garcia-Rodenas, C. L. Tags: REVIEW Source Type: research

Plasticity of neuroeffector transmission during bowel inflammation1
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. The net result is a breakdown in the precisely orchestrated coordination of motility, fluid secret...
Source: AJP: Gastrointestinal and Liver Physiology - February 28, 2017 Category: Gastroenterology Authors: Lomax, A. E., Pradhananga, S., Bertrand, P. P. Tags: THEMES Source Type: research

Computational modeling of epithelial fluid and ion transport in the parotid duct after transfection of human aquaporin-1
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 electrochemistry 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 measureme...
Source: AJP: Gastrointestinal and Liver Physiology - February 6, 2017 Category: Gastroenterology Authors: Fong, S., Chiorini, J. A., Sneyd, J., Suresh, V. Tags: RESEARCH ARTICLE Source Type: research

Potential roles of enteric glia in bridging neuroimmune communication in the gut
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. Because of the proximity of the ENS to bacteria and other foreign antigens in the GI tract, it is important to prevent the passage of these antigens through the GI epithelium. If any foreign compounds manage to pass through the GI ep...
Source: AJP: Gastrointestinal and Liver Physiology - February 6, 2017 Category: Gastroenterology Authors: Chow, A. K., Gulbransen, B. D. Tags: THEMES Source Type: research

NOTCH1 and NOTCH2 regulate epithelial cell proliferation in mouse and human gastric corpus
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. Global Notch inhibition for 5 days reduced progenitor cell proliferation in the mouse corpus, as well as in organoids derived from mouse and human corpus tissue. Proliferation effects were mediated through both NOTCH1 and NOTCH2 recept...
Source: AJP: Gastrointestinal and Liver Physiology - January 31, 2017 Category: Gastroenterology Authors: Demitrack, E. S., Gifford, G. B., Keeley, T. M., Horita, N., Todisco, A., Turgeon, D. K., Siebel, C. W., Samuelson, L. C. Tags: RESEARCH ARTICLE Source Type: research

miR-200b inhibits TNF-{alpha}-induced IL-8 secretion and tight junction disruption of intestinal epithelial cells in vitro
In this study, we further investigated the impact of miR-200b on intestinal epithelial inflammation and tight junctions in two distinct differentiated states of Caco-2 cells after TNF-α treatment. We demonstrated that TNF-α-enhanced IL-8 expression was decreased by microRNA (miR)-200b in undifferentiated IECs. Simultaneously, miR-200b could alleviate TNF-α-induced tight junction (TJ) disruption in well-differentiated IECs by reducing the reduction in the transepithelial electrical resistance (TEER), inhibiting the increase in paracellular permeability, and preventing the morphological redistribution of th...
Source: AJP: Gastrointestinal and Liver Physiology - January 31, 2017 Category: Gastroenterology Authors: Shen, Y., Zhou, M., Yan, J., Gong, Z., Xiao, Y., Zhang, C., Du, P., Chen, Y. Tags: RESEARCH ARTICLE Source Type: research

Critical role of microbiota within cecal crypts on the regenerative capacity of the intestinal epithelium following surgical stress
This study provides novel insight into the process by which surgical injury places the intestinal epithelium at risk for colonization by pathogenic microbes and impairment of its regenerative capacity via loss of its microbiota. We show that fecal transplant restores crypt homeostasis in association with repopulation of the microbiota within cecal crypts. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - January 31, 2017 Category: Gastroenterology Authors: Zaborin, A., Krezalek, M., Hyoju, S., Defazio, J. R., Setia, N., Belogortseva, N., Bindokas, V. P., Guo, Q., Zaborina, O., Alverdy, J. C. Tags: RESEARCH ARTICLE Source Type: research

Neuropeptide Y (NPY) promotes inflammation-induced tumorigenesis by enhancing epithelial cell proliferation
We have demonstrated that neuropeptide Y (NPY), abundantly produced by enteric neurons, is an important regulator of intestinal inflammation. However, the role of NPY in the progression of chronic inflammation to tumorigenesis is unknown. We investigated whether NPY could modulate epithelial cell proliferation and apoptosis, and thus regulate tumorigenesis. Repeated cycles of dextran sodium sulfate (DSS) were used to model inflammation-induced tumorigenesis in wild-type (WT) and NPY knockout (NPY–/–) mice. Intestinal epithelial cell lines (T84) were used to assess the effects of NPY (0.1 µM) on epithelial...
Source: AJP: Gastrointestinal and Liver Physiology - January 31, 2017 Category: Gastroenterology Authors: Jeppsson, S., Srinivasan, S., Chandrasekharan, B. Tags: RESEARCH ARTICLE Source Type: research