Hepatocellular autophagy modulates the unfolded protein response and fasting-induced steatosis in mice
Autophagy and the unfolded protein response (UPR) are key cellular homeostatic mechanisms and are both involved in liver diseases, including nonalcoholic fatty liver disease (NAFLD). Although increasing but conflicting results link these mechanisms to lipid metabolism, their role and potential cross talk herein have been poorly investigated. Therefore, we assessed the effects of hepatocyte-specific autophagy deficiency on liver parenchyma, the UPR, and lipid metabolism. Adult hepatocellular-specific autophagy-deficient mice (Atg7F/FAlb-Cre+) were compared with their autophagy-competent littermates (Atg7+/+Alb-Cre+). Livers...
Source: AJP: Gastrointestinal and Liver Physiology - September 30, 2016 Category: Gastroenterology Authors: Kwanten, W. J., Vandewynckel, Y.-P., Martinet, W., De Winter, B. Y., Michielsen, P. P., Van Hoof, V. O., Driessen, A., Timmermans, J.-P., Bedossa, P., Van Vlierberghe, H., Francque, S. M. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

The kielin/chordin-like protein KCP attenuates nonalcoholic fatty liver disease in mice
In this report, we show that aging KCP mutant (Kcp–/–) mice are increasingly susceptible to developing hepatic steatosis and liver fibrosis. When young mice are put on a high-fat diet, Kcp–/– mice are also more susceptible to developing liver pathology, compared with their wild-type littermates. Furthermore, mice that express a Pepck-KCP transgene (KcpTg) in the liver are resistant to developing liver pathology even when fed a high-fat diet. Analyses of liver tissues reveal a significant reduction of P-Smad3, consistent with a role for KCP in suppressing TGF-β signaling. Transcriptome analyses ...
Source: AJP: Gastrointestinal and Liver Physiology - September 30, 2016 Category: Gastroenterology Authors: Soofi, A., Wolf, K. I., Ranghini, E. J., Amin, M. A., Dressler, G. R. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Ion channelopathies in functional GI disorders
In the gastrointestinal (GI) tract, abnormalities in secretion, absorption, motility, and sensation have been implicated in functional gastrointestinal disorders (FGIDs). Ion channels play important roles in all these GI functions. Disruptions of ion channels' ability to conduct ions can lead to diseases called ion channelopathies. Channelopathies can result from changes in ion channel biophysical function or expression due to mutations, posttranslational modification, and accessory protein malfunction. Channelopathies are strongly established in the fields of cardiology and neurology, but ion channelopathies are only begi...
Source: AJP: Gastrointestinal and Liver Physiology - September 30, 2016 Category: Gastroenterology Authors: Beyder, A., Farrugia, G. Tags: MINIREVIEW Source Type: research

Identification of food-grade subtilisins as gluten-degrading enzymes to treat celiac disease
This study identified Rothia and food-grade Bacillus subtilisins as promising new candidates for enzyme therapeutics in CD. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - September 8, 2016 Category: Gastroenterology Authors: Wei, G., Tian, N., Siezen, R., Schuppan, D., Helmerhorst, E. J. Tags: MICROBIOME AND HOST INTERACTIONS Source Type: research

Role of the sodium-dependent multivitamin transporter (SMVT) in the maintenance of intestinal mucosal integrity
Utilizing a conditional (intestinal-specific) knockout (cKO) mouse model, we have recently shown that the sodium-dependent multivitamin transporter (SMVT) (SLC5A6) is the only biotin uptake system that operates in the gut and that its deletion leads to biotin deficiency. Unexpectedly, we also observed that all SMVT-cKO mice develop chronic active inflammation, especially in the cecum. Our aim here was to examine the role of SMVT in the maintenance of intestinal mucosal integrity [permeability and expression of tight junction (TJ) proteins]. Our results showed that knocking out the mouse intestinal SMVT is associated with a...
Source: AJP: Gastrointestinal and Liver Physiology - September 8, 2016 Category: Gastroenterology Authors: Sabui, S., Bohl, J. A., Kapadia, R., Cogburn, K., Ghosal, A., Lambrecht, N. W., Said, H. M. Tags: NUTRIENT SENSING, NUTRITION, AND METABOLISM Source Type: research

Legumain is activated in macrophages during pancreatitis
Pancreatitis is an inflammatory disease of the pancreas characterized by dysregulated activity of digestive enzymes, necrosis, immune infiltration, and pain. Repeated incidence of pancreatitis is an important risk factor for pancreatic cancer. Legumain, a lysosomal cysteine protease, has been linked to inflammatory diseases such as atherosclerosis, stroke, and cancer. Until now, legumain activation has not been studied during pancreatitis. We used a fluorescently quenched activity-based probe to assess legumain activation during caerulein-induced pancreatitis in mice. We detected activated legumain by ex vivo imaging, conf...
Source: AJP: Gastrointestinal and Liver Physiology - September 8, 2016 Category: Gastroenterology Authors: Edgington-Mitchell, L. E., Wartmann, T., Fleming, A. K., Gocheva, V., van der Linden, W. A., Withana, N. P., Verdoes, M., Aurelio, L., Edgington-Mitchell, D., Lieu, T., Parker, B. S., Graham, B., Reinheckel, T., Furness, J. B., Joyce, J. A., Storz, P., Ha Tags: PANCREATIC PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Macrophage colony-stimulating factor (CSF1) controls monocyte production and maturation and the steady-state size of the liver in pigs
Macrophage colony-stimulating factor (CSF1) is an essential growth and differentiation factor for cells of the macrophage lineage. To explore the role of CSF1 in steady-state control of monocyte production and differentiation and tissue repair, we previously developed a bioactive protein with a longer half-life in circulation by fusing pig CSF1 with the Fc region of pig IgG1a. CSF1-Fc administration to pigs expanded progenitor pools in the marrow and selectively increased monocyte numbers and their expression of the maturation marker CD163. There was a rapid increase in the size of the liver, and extensive proliferation of...
Source: AJP: Gastrointestinal and Liver Physiology - September 8, 2016 Category: Gastroenterology Authors: Sauter, K. A., Waddell, L. A., Lisowski, Z. M., Young, R., Lefevre, L., Davis, G. M., Clohisey, S. M., McCulloch, M., Magowan, E., Mabbott, N. A., Summers, K. M., Hume, D. A. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model
Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation w...
Source: AJP: Gastrointestinal and Liver Physiology - September 8, 2016 Category: Gastroenterology Authors: Yu, Y., Lu, L., Sun, J., Petrof, E. O., Claud, E. C. Tags: TRANSLATIONAL PHYSIOLOGY Source Type: research

How host regulation of Helicobacter pylori-induced gastritis protects against peptic ulcer disease and gastric cancer
The bacterial pathogen Helicobacter pylori is the etiological agent of a range of gastrointestinal pathologies including peptic ulcer disease and the major killer, gastric adenocarcinoma. Infection with this bacterium induces a chronic inflammatory response in the gastric mucosa (gastritis). It is this gastritis that, over decades, eventually drives the development of H. pylori-associated disease in some individuals. The majority of studies investigating H. pylori pathogenesis have focused on factors that promote disease development in infected individuals. However, an estimated 85% of those infected with H. pylori remain ...
Source: AJP: Gastrointestinal and Liver Physiology - September 8, 2016 Category: Gastroenterology Authors: Dhar, P., Ng, G. Z., Sutton, P. Tags: REVIEW Source Type: research

Opioidergic effects on enteric and sensory nerves in the lower GI tract: basic mechanisms and clinical implications
Opioids are one of the most prescribed drug classes for treating acute pain. However, chronic use is often associated with tolerance as well as debilitating side effects, including nausea and dependence, which are mediated by the central nervous system, as well as constipation emerging from effects on the enteric nervous system. These gastrointestinal (GI) side effects limit the usefulness of opioids in treating pain in many patients. Understanding the mechanism(s) of action of opioids on the nervous system that shows clinical benefit as well as those that have unwanted effects is critical for the improvement of opioid dru...
Source: AJP: Gastrointestinal and Liver Physiology - September 8, 2016 Category: Gastroenterology Authors: Hughes, P. A., Costello, S. P., Bryant, R. V., Andrews, J. M. Tags: REVIEW Source Type: research

Malabsorption and intestinal adaptation after one anastomosis gastric bypass compared with Roux-en-Y gastric bypass in rats
In this study, we compared macronutrient absorption and intestinal adaptation after MGB or RYGB in rats. Body weight and food intake were monitored and glucose tolerance tests were performed in rats subjected to MGB, RYGB, or sham surgery. Carbohydrate, protein, and lipid absorption was determined by fecal analyses. Intestinal remodeling was evaluated by histology and immunohistochemistry. Peptide and amino acid transporter mRNA levels were measured in the remodeled intestinal mucosa and those of anorexigenic and orexigenic peptides in the hypothalamus. The MGB and RYGB surgeries both resulted in a reduction of body weight...
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Cavin, J.-B., Voitellier, E., Cluzeaud, F., Kapel, N., Marmuse, J.-P., Chevallier, J.-M., Msika, S., Bado, A., Le Gall, M. Tags: NUTRIENT SENSING, NUTRITION, AND METABOLISM Source Type: research

Bovine colostrum improves neonatal growth, digestive function, and gut immunity relative to donor human milk and infant formula in preterm pigs
Mother's own milk is the optimal first diet for preterm infants, but donor human milk (DM) or infant formula (IF) is used when supply is limited. We hypothesized that a gradual introduction of bovine colostrum (BC) or DM improves gut maturation, relative to IF during the first 11 days after preterm birth. Preterm pigs were fed gradually advancing doses of BC, DM, or IF (3–15 ml·kg–1·3 h–1, n = 14–18) before measurements of gut structure, function, microbiology, and immunology. The BC pigs showed higher body growth, intestinal hexose uptake, and transit time and reduced diarrhea and gut...
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Rasmussen, S. O., Martin, L., Ostergaard, M. V., Rudloff, S., Li, Y., Roggenbuck, M., Bering, S. B., Sangild, P. T. Tags: NUTRIENT SENSING, NUTRITION, AND METABOLISM Source Type: research

The serine protease-mediated increase in intestinal epithelial barrier function is dependent on occludin and requires an intact tight junction
Barrier dysfunction is a characteristic of the inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Understanding how the tight junction is modified to maintain barrier function may provide avenues for treatment of IBD. We have previously shown that the apical addition of serine proteases to intestinal epithelial cell lines causes a rapid and sustained increase in transepithelial electrical resistance (TER), but the mechanisms are unknown. We hypothesized that serine proteases increase barrier function through trafficking and insertion of tight junction proteins into the membrane, and this could enhan...
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Ronaghan, N. J., Shang, J., Iablokov, V., Zaheer, R., Colarusso, P., Turner, J. R., MacNaughton, W. K. Tags: EPITHELIAL BIOLOGY AND SECRETION Source Type: research

Redox control of Cas phosphorylation requires Abl kinase in regulation of intestinal epithelial cell spreading and migration
Intestinal wounds often occur during inflammatory and ischemic disorders of the gut. To repair damage, intestinal epithelial cells must rapidly spread and migrate to cover exposed lamina propria, events that involve redox signaling. Wounds are subject to extensive redox alterations, particularly resulting from H2O2 produced in the adjacent tissue by both the epithelium and emigrating leukocytes. The mechanisms governing these processes are not fully understood, particularly at the level of protein signaling. Crk-associated substrate, or Cas, is an important signaling protein known to modulate focal adhesion and actin cytos...
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Matthews, J. D., Sumagin, R., Hinrichs, B., Nusrat, A., Parkos, C. A., Neish, A. S. Tags: EPITHELIAL BIOLOGY AND SECRETION Source Type: research

A long noncoding RNA signature for ulcerative colitis identifies IFNG-AS1 as an enhancer of inflammation
High-throughput technologies revealed new categories of genes, including the long noncoding RNAs (lncRNAs), involved in the pathogenesis of human disease; however, the role of lncRNAs in the ulcerative colitis (UC) has not been evaluated. Gene expression profiling was used to develop lncRNA signatures in UC samples. Jurkat T cells were activated by PMA/ionomycin subsequently interferon- (IFNG) and tumor necrosis factor (TNF)-α protein levels were assessed by ELISA. Anti-sense molecules were designed to block IFNG-AS1 expression. A unique set of lncRNAs was differentially expressed between UC and control samples. Of t...
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Padua, D., Mahurkar-Joshi, S., Law, I. K. M., Polytarchou, C., Vu, J. P., Pisegna, J. R., Shih, D., Iliopoulos, D., Pothoulakis, C. Tags: INFLAMMATION, IMMUNITY, AND INFECTION Source Type: research