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.

Long non-coding RNA NEAT1 promotes hepatocellular carcinoma cell proliferation through the regulation of miR-129-5p-VCP-I{kappa}B
This study provides new insights into the pathogenesis of HCC, as well as identifying new target genes for diagnosis and treatment. NEW & NOTEWORTHY The results provide strong evidence that upregulated NEAT1 promotes the proliferation of cancer cells in hepatocellular carcinoma (HCC) and this regulatory mechanism depends on the microRNA (miR)-129-5p-valosin-containing protein-IB axis. The study also indicates that NEAT1 could be a potential therapeutic target for HCC. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - August 1, 2017 Category: Gastroenterology Authors: Fang, L., Sun, J., Pan, Z., Song, Y., Zhong, L., Zhang, Y., Liu, Y., Zheng, X., Huang, P. Tags: RESEARCH ARTICLE Source Type: research

CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma
CD151, a member of the tetraspanin family of receptors, is a lateral organizer and modulator of activity of several families of transmembrane proteins. It has been implicated in the development and progression of several cancers, but its role in chronic inflammatory disease is less well understood. Here we show that CD151 is upregulated by distinct microenvironmental signals in a range of chronic inflammatory liver diseases and in primary liver cancer, in which it supports lymphocyte recruitment. CD151 was highly expressed in endothelial cells of the hepatic sinusoids and neovessels developing in fibrotic septa and tumor m...
Source: AJP: Gastrointestinal and Liver Physiology - August 1, 2017 Category: Gastroenterology Authors: Wadkin, J. C. R., Patten, D. A., Kamarajah, S. K., Shepherd, E. L., Novitskaya, V., Berditchevski, F., Adams, D. H., Weston, C. J., Shetty, S. Tags: RESEARCH ARTICLE Source Type: research

A common NHE3 single-nucleotide polymorphism has normal function and sensitivity to regulatory ligands
This study reports results on the functional significance of human NHE3-799C under basal conditions and in response to regulatory ligands, including a novel NHE3 inhibitor called tenapanor. We demonstrate that NHE3-799C is a common variant of NHE3 that is enriched in Asian populations; however, in contrast to our previous studies using rabbit NHE3, its presence seems to have limited clinical significance in humans and is not associated with compromised function or abnormal transport regulation. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - August 1, 2017 Category: Gastroenterology Authors: Yin, J., Tse, C.-M., Cha, B., Sarker, R., Zhu, X. C., Walentinsson, A., Greasley, P. J., Donowitz, M. Tags: RESEARCH ARTICLE Source Type: research

FFA2 activation combined with ulcerogenic COX inhibition induces duodenal mucosal injury via the 5-HT pathway in rats
Serotonin (5-HT), predominantly synthesized and released by enterochromaffin cells, is implicated in gastrointestinal symptoms such as emesis, abdominal pain, and diarrhea. Because luminal short-chain fatty acids (SCFAs) release 5-HT from enterochromaffin cells, which express the SCFA receptor free fatty acid receptor 2 (FFA2) in rat duodenum, we examined the effects of the selective FFA2 agonist phenylacetamide-1 (PA1) on duodenal 5-HT release with consequent bicarbonate secretion [duodenal bicarbonate secretion (DBS)] and on indomethacin (IND)-induced enteropathy. Intestinal injury was induced by IND (10 mg/kg sc) with o...
Source: AJP: Gastrointestinal and Liver Physiology - August 1, 2017 Category: Gastroenterology Authors: Akiba, Y., Maruta, K., Narimatsu, K., Said, H., Kaji, I., Kuri, A., Iwamoto, K.-i., Kuwahara, A., Kaunitz, J. D. Tags: RESEARCH ARTICLE Source Type: research

Emerging concepts in biliary repair and fibrosis
Chronic diseases of the biliary tree (cholangiopathies) represent one of the major unmet needs in clinical hepatology and a significant knowledge gap in liver pathophysiology. The common theme in cholangiopathies is that the target of the disease is the biliary tree. After damage to the biliary epithelium, inflammatory changes stimulate a reparative response with proliferation of cholangiocytes and restoration of the biliary architecture, owing to the reactivation of a variety of morphogenetic signals. Chronic damage and inflammation will ultimately result in pathological repair with generation of biliary fibrosis and clin...
Source: AJP: Gastrointestinal and Liver Physiology - August 1, 2017 Category: Gastroenterology Authors: Fabris, L., Spirli, C., Cadamuro, M., Fiorotto, R., Strazzabosco, M. Tags: REVIEW Source Type: research

The emerging role of mast cells in liver disease
The depth of our knowledge regarding mast cells has widened exponentially in the last 20 years. Once thought to be only important for allergy-mediated events, mast cells are now recognized to be important regulators of a number of pathological processes. The revelation that mast cells can influence organs, tissues, and cells has increased interest in mast cell research during liver disease. The purpose of this review is to refresh the reader’s knowledge of the development, type, and location of mast cells and to review recent work that demonstrates the role of hepatic mast cells during diseased states. This review fo...
Source: AJP: Gastrointestinal and Liver Physiology - August 1, 2017 Category: Gastroenterology Authors: Jarido, V., Kennedy, L., Hargrove, L., Demieville, J., Thomson, J., Stephenson, K., Francis, H. Tags: REVIEW Source Type: research

Human-derived gut microbiota modulates colonic secretion in mice by regulating 5-HT3 receptor expression via acetate production
In this study, we determine whether human-derived gut microbiota affects host secretory response to 5-HT and 5-HT receptor expression. We used proximal colonic mucosa-submucosa preparation from age-matched Swiss Webster germ-free (GF) and humanized (HM; ex-GF colonized with human gut microbiota) mice. 5-HT evoked a significantly greater increase in short-circuit current (Isc) in GF compared with HM mice. Additionally, 5-HT3 receptor mRNA and protein expression was significantly higher in GF compared with HM mice. Ondansetron, a 5-HT3 receptor antagonist, inhibited 5-HT-evoked Isc in GF mice but not in HM mice. Furthermore,...
Source: AJP: Gastrointestinal and Liver Physiology - July 1, 2017 Category: Gastroenterology Authors: Bhattarai, Y., Schmidt, B. A., Linden, D. R., Larson, E. D., Grover, M., Beyder, A., Farrugia, G., Kashyap, P. C. Tags: RESEARCH ARTICLE Source Type: research

Elevated intrabolus pressure identifies obstructive processes when integrated relaxation pressure is normal on esophageal high-resolution manometry
Elevated integrated relaxation pressure (IRP) on esophageal high-resolution manometry (HRM) identifies obstructive processes at the esophagogastric junction (EGJ). Our aim was to determine whether intrabolus pressure (IBP) can identify structural EGJ processes when IRP is normal. In this observational cohort study, adult patients with dysphagia and undergoing HRM were evaluated for endoscopic evidence of structural EGJ processes (strictures, rings, hiatus hernia) in the setting of normal IRP. HRM metrics [IRP, distal contractile integral (DCI), distal latency (DL), IBP, and EGJ contractile integral (EGJ-CI)] were compared ...
Source: AJP: Gastrointestinal and Liver Physiology - July 1, 2017 Category: Gastroenterology Authors: Quader, F., Reddy, C., Patel, A., Gyawali, C. P. Tags: RESEARCH ARTICLE Source Type: research

Gastroparesis and lipid metabolism-associated dysbiosis in Wistar-Kyoto rats
This study reveals that the stress-prone Wistar-Kyoto rat strain has a baseline physiology of gastroparesis and rapid small intestine transit, together with metabolic changes consistent with lipid metabolism-associated dysbiosis, compared with nonstress-prone rats. This suggests that the Wistar-Kyoto rat strain may be an appropriate animal model for gastroparesis. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - July 1, 2017 Category: Gastroenterology Authors: Dalziel, J. E., Fraser, K., Young, W., McKenzie, C. M., Bassett, S. A., Roy, N. C. Tags: RESEARCH ARTICLE Source Type: research

Phosphatidylcholine transfer protein/StarD2 promotes microvesicular steatosis and liver injury in murine experimental steatohepatitis
This study identifies a pathogenic role for PC-TP, independent of Them2, in the methionine- and choline-deficient diet model of experimental steatohepatitis. Our current observations suggest that PC-TP promotes liver injury by mediating the intermembrane transfer of phosphatidylcholines, thus stabilizing more pathogenic microvesicular lipid droplets. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - July 1, 2017 Category: Gastroenterology Authors: Nicholls, H. T., Hornick, J. L., Cohen, D. E. Tags: RESEARCH ARTICLE Source Type: research

Targeted inactivation of copper transporter Atp7b in hepatocytes causes liver steatosis and obesity in mice
Copper-transporting ATPase 2 (ATP7B) is essential for mammalian copper homeostasis. Mutations in ATP7B result in copper accumulation, especially in the liver, and cause Wilson disease (WD). The major role of hepatocytes in WD pathology is firmly established. It is less certain whether the excess Cu in hepatocytes is solely responsible for development of WD. To address this issue, we generated a mouse strain for Cre-mediated deletion of Atp7b and inactivated Atp7b selectively in hepatocytes. Atp7bHep mice accumulate copper in the liver, have elevated urinary copper, and lack holoceruloplasmin but show no liver disease for u...
Source: AJP: Gastrointestinal and Liver Physiology - July 1, 2017 Category: Gastroenterology Authors: Muchenditsi, A., Yang, H., Hamilton, J. P., Koganti, L., Housseau, F., Aronov, L., Fan, H., Pierson, H., Bhattacharjee, A., Murphy, R., Sears, C., Potter, J., Wooton-Kee, C. R., Lutsenko, S. Tags: RESEARCH ARTICLE Source Type: research

Absence of the NOD2 protein renders epithelia more susceptible to barrier dysfunction due to mitochondrial dysfunction
Irregular mitochondria structure and reduced ATP in some patients with IBD suggest that metabolic stress contributes to disease. Loss-of-function mutation in the nucleotide-binding oligomerization domain (NOD)-2 gene is a major susceptibility trait for IBD. Hence, we assessed if loss of NOD2 further impairs the epithelial barrier function instigated by disruption of mitochondrial ATP synthesis via the hydrogen ionophore dinitrophenol (DNP). NOD2 protein (virtually undetectable in epithelia under basal conditions) was increased in T84 (human colon cell line) cells treated with noninvasive Escherichia coli + DNP (16 h). Incr...
Source: AJP: Gastrointestinal and Liver Physiology - July 1, 2017 Category: Gastroenterology Authors: Saxena, A., Lopes, F., Poon, K. K. H., McKay, D. M. Tags: RESEARCH ARTICLE Source Type: research

Expression and localization of VPAC1, the major receptor of vasoactive intestinal peptide along the length of the intestine
Vasoactive intestinal peptide (VIP) is an endogenous neuropeptide with a broad array of physiological functions in many organs including the intestine. Its actions are mediated via G protein-coupled receptors, and vasoactive intestinal peptide receptor 1 (VPAC1) is the key receptor responsible for majority of VIP’s biological activity. The distribution of VPAC1 along the length of the gastrointestinal tract and its subcellular localization in intestinal epithelial cells have not been fully characterized. The current studies were undertaken to determine VPAC1 distribution and localization so that VIP-based therapies c...
Source: AJP: Gastrointestinal and Liver Physiology - July 1, 2017 Category: Gastroenterology Authors: Jayawardena, D., Guzman, G., Gill, R. K., Alrefai, W. A., Onyuksel, H., Dudeja, P. K. Tags: RESEARCH ARTICLE Source Type: research

A new role for microbiota? Dulling the thrust of serotonin and 5-HT3 signaling cascade
(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - July 1, 2017 Category: Gastroenterology Authors: Chang, E. B., Rao, M. C. Tags: EDITORIAL FOCUS Source Type: research

From sensing to shaping microbiota: insights into the role of NOD2 in intestinal homeostasis and progression of Crohns disease
NOD2 was the first susceptibility gene identified for Crohn’s disease (CD), one of the major forms of inflammatory bowel disease (IBD). The field of NOD2 research has opened up many questions critical to understanding the complexities of microbiota-host interactions. In addition to sensing its specific bacterial components as a cytosolic pattern recognition receptor, NOD2 also appears to shape the colonization of intestinal microbiota. Activated NOD2 triggers downstream signaling cascades exampled by the NF-B pathway to induce antimicrobial activities, however, defective or loss of NOD2 functions incur a similarly ac...
Source: AJP: Gastrointestinal and Liver Physiology - July 1, 2017 Category: Gastroenterology Authors: Balasubramanian, I., Gao, N. Tags: MINI-REVIEW Source Type: research