Platelet interaction with lymphatics aggravates intestinal inflammation by suppressing lymphangiogenesis
Lymphatic failure is a histopathological feature of inflammatory bowel disease (IBD). Recent studies show that interaction between platelets and podoplanin on lymphatic endothelial cells (LECs) suppresses lymphangiogenesis. We aimed to investigate the role of platelets in the inflammatory process of colitis, which is likely to be through modulation of lymphangiogenesis. Lymphangiogenesis in colonic mucosal specimens from patients with IBD was investigated by studying mRNA expression of lymphangiogenic factors and histologically by examining lymphatic vessel (LV) densities. Involvement of lymphangiogenesis in intestinal inf...
Source: AJP: Gastrointestinal and Liver Physiology - July 31, 2016 Category: Gastroenterology Authors: Sato, H., Higashiyama, M., Hozumi, H., Sato, S., Furuhashi, H., Takajo, T., Maruta, K., Yasutake, Y., Narimatsu, K., Yoshikawa, K., Kurihara, C., Okada, Y., Watanabe, C., Komoto, S., Tomita, K., Nagao, S., Miura, S., Hokari, R. Tags: INFLAMMATION, IMMUNITY, AND INFECTION Source Type: research

Hepatocyte nuclear factor 4{alpha} is required for cell differentiation and homeostasis in the adult mouse gastric epithelium
We have previously shown that the sequential transcription factors Xbp1->Mist1 (Bhlha15) govern the ultrastructural maturation of the secretory apparatus in enzyme-secreting zymogenic chief cells (ZCs) in the gastric unit. Here we sought to identify transcriptional regulators upstream of X-box binding protein 1 (XBP1) and MIST1. We used immunohistochemistry to characterize Hnf4αflox/flox adult mouse stomachs after tamoxifen-induced deletion of Hnf4α. We used qRT-PCR, Western blotting, and chromatin immunoprecipitation to define the molecular interaction between hepatocyte nuclear factor 4 alpha (HNF4α)...
Source: AJP: Gastrointestinal and Liver Physiology - July 31, 2016 Category: Gastroenterology Authors: Moore, B. D., Khurana, S. S., Huh, W. J., Mills, J. C. Tags: STEM CELLS, TISSUE ENGINEERING, DEVELOPMENT, AND CANCER Source Type: research

Distribution and trafficking of the {mu}-opioid receptor in enteric neurons of the guinea pig
The μ-opioid receptor (MOR) is a major regulator of gastrointestinal motility and secretion and mediates opiate-induced bowel dysfunction. Although MOR is of physiological and therapeutic importance to gut function, the cellular and subcellular distribution and regulation of MOR within the enteric nervous system are largely undefined. Herein, we defined the neurochemical coding of MOR-expressing neurons in the guinea pig gut and examined the effects of opioids on MOR trafficking and regulation. MOR expression was restricted to subsets of enteric neurons. In the stomach MOR was mainly localized to nitrergic neurons (~88%...
Source: AJP: Gastrointestinal and Liver Physiology - July 31, 2016 Category: Gastroenterology Authors: Lay, J., Carbone, S. E., DiCello, J. J., Bunnett, N. W., Canals, M., Poole, D. P. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

Angiocrine signaling in the hepatic sinusoids in health and disease
The capillary network irrigating the liver is important not only for nutrient and oxygen delivery, but also for the signals distributed to other hepatic cell types necessary to maintain liver homeostasis. During development, endothelial cells are a key component in liver zonation. In adulthood, they maintain hepatic stellate cells and hepatocytes in quiescence. Their importance in pathobiology is highlighted in liver regeneration and chronic liver diseases, where they coordinate paracrine cell behavior. During regeneration, liver sinusoidal endothelial cells induce hepatocyte proliferation and angiogenesis. During fibrogen...
Source: AJP: Gastrointestinal and Liver Physiology - July 31, 2016 Category: Gastroenterology Authors: Kostallari, E., Shah, V. H. Tags: PERSPECTIVES Source Type: research

Contribution of programmed cell death receptor (PD)-1 to Kupffer cell dysfunction in murine polymicrobial sepsis
Recent studies suggest that coinhibitory receptors appear to be important in contributing sepsis-induced immunosuppression. Our laboratory reported that mice deficient in programmed cell death receptor (PD)-1 have increased bacterial clearance and improved survival in experimental sepsis induced by cecal ligation and puncture (CLP). In response to infection, the liver clears the blood of bacteria and produces cytokines. Kupffer cells, the resident macrophages in the liver, are strategically situated to perform the above functions. However, it is not known if PD-1 expression on Kupffer cells is altered by septic stimuli, le...
Source: AJP: Gastrointestinal and Liver Physiology - July 31, 2016 Category: Gastroenterology Authors: Wang, F., Huang, X., Chung, C.-S., Chen, Y., Hutchins, N. A., Ayala, A. Tags: INFLAMMATION, IMMUNITY, AND INFECTION Source Type: research

PAR2-dependent activation of GSK3{beta} regulates the survival of colon stem/progenitor cells
Protease-activated receptors PAR1 and PAR2 play an important role in the control of epithelial cell proliferation and migration. However, the survival of normal and tumor intestinal stem/progenitor cells promoted by proinflammatory mediators may be critical in oncogenesis. The glycogen synthase kinase-3β (GSK3β) pathway is overactivated in colon cancer cells and promotes their survival and drug resistance. We thus aimed to determine PAR1 and PAR2 effects on normal and tumor intestinal stem/progenitor cells and whether they involved GSK3β. First, PAR1 and PAR2 were identified in colon stem/progenitor cells by...
Source: AJP: Gastrointestinal and Liver Physiology - July 31, 2016 Category: Gastroenterology Authors: Nasri, I., Bonnet, D., Zwarycz, B., d'Aldebert, E., Khou, S., Mezghani-Jarraya, R., Quaranta, M., Rolland, C., Bonnart, C., Mas, E., Ferrand, A., Cenac, N., Magness, S., Van Landeghem, L., Vergnolle, N., Racaud-Sultan, C. Tags: STEM CELLS, TISSUE ENGINEERING, DEVELOPMENT, AND CANCER Source Type: research

High-fat diet-induced obesity alters nitric oxide-mediated neuromuscular transmission and smooth muscle excitability in the mouse distal colon
We tested the hypothesis that colonic enteric neurotransmission and smooth muscle cell (SMC) function are altered in mice fed a high-fat diet (HFD). We used wild-type (WT) mice and mice lacking the β1-subunit of the BK channel (BKβ1–/–). WT mice fed a HFD had increased myenteric plexus oxidative stress, a 28% decrease in nitrergic neurons, and a 20% decrease in basal nitric oxide (NO) levels. Circular muscle inhibitory junction potentials (IJPs) were reduced in HFD WT mice. The NO synthase inhibitor nitro-l-arginine (NLA) was less effective at inhibiting relaxations in HFD compared with control diet (...
Source: AJP: Gastrointestinal and Liver Physiology - July 31, 2016 Category: Gastroenterology Authors: Bhattarai, Y., Fried, D., Gulbransen, B., Kadrofske, M., Fernandes, R., Xu, H., Galligan, J. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

Stromal cell-derived factor-1 (SDF-1) as a target in liver diseases
The chemokine stromal cell-derived factor-1 (SDF-1) or CXCL12 is constitutively expressed in healthy liver. However, its expression increases following acute or chronic liver injury. Liver sinusoidal endothelial cells (LSEC), hepatic stellate cells (HSC), and malignant hepatocytes are important sources of SDF-1/CXCL12 in liver diseases. CXCL12 is able to activate two chemokine receptors with different downstream signaling pathways, CXCR4 and CXCR7. CXCR7 expression is relevant on LSEC, while HSC, mesenchymal stem cells, and tumor cells mainly respond via CXCR4. Here, we summarize recent developments in the field of liver d...
Source: AJP: Gastrointestinal and Liver Physiology - July 31, 2016 Category: Gastroenterology Authors: Liepelt, A., Tacke, F. Tags: MINIREVIEW Source Type: research

Corrigendum
(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - July 12, 2016 Category: Gastroenterology Tags: CORRIGENDUM Source Type: research

Night workers with circadian misalignment are susceptible to alcohol-induced intestinal hyperpermeability with social drinking
Alcohol-induced intestinal hyperpermeability (AIHP) is a known risk factor for alcoholic liver disease (ALD), but only 20–30% of heavy alcoholics develop AIHP and ALD. The hypothesis of this study is that circadian misalignment would promote AIHP. We studied two groups of healthy subjects on a stable work schedule for 3 mo [day workers (DW) and night workers (NW)]. Subjects underwent two circadian phase assessments with sugar challenge to access intestinal permeability between which they drank 0.5 g/kg alcohol daily for 7 days. Sleep architecture by actigraphy did not differ at baseline or after alcohol between eithe...
Source: AJP: Gastrointestinal and Liver Physiology - July 12, 2016 Category: Gastroenterology Authors: Swanson, G. R., Gorenz, A., Shaikh, M., Desai, V., Kaminsky, T., Van Den Berg, J., Murphy, T., Raeisi, S., Fogg, L., Vitaterna, M. H., Forsyth, C., Turek, F., Burgess, H. J., Keshavarzian, A. Tags: TRANSLATIONAL HUMAN PATHOPHYSIOLOGY Source Type: research

Effect of liposome-encapsulated hemoglobin resuscitation on proteostasis in small intestinal epithelium after hemorrhagic shock
The objective of this study was to investigate whether resuscitation with nanoparticulate liposome-encapsulated hemoglobin (LEH) is able to restore the gut proteostatic mechanisms. Sprague-Dawley rats were recruited in four groups: control, HS, HS+LEH, and HS+saline. HS was induced by withdrawing 45% blood, and isovolemic LEH or saline was administered after 15 min of shock. The rats were euthanized at 6 h to collect plasma and ileum for measurement of the markers of oxidative stress, unfolded protein response (UPR), proteasome function, and autophagy. HS significantly increased the protein and lipid oxidation, trypsin-lik...
Source: AJP: Gastrointestinal and Liver Physiology - July 12, 2016 Category: Gastroenterology Authors: Rao, G., Yadav, V. R., Awasthi, S., Roberts, P. R., Awasthi, V. Tags: INFLAMMATION, IMMUNITY, AND INFECTION Source Type: research

Gut microbiota are linked to increased susceptibility to hepatic steatosis in low-aerobic-capacity rats fed an acute high-fat diet
Poor aerobic fitness is linked to nonalcoholic fatty liver disease and increased all-cause mortality. We previously found that rats with a low capacity for running (LCR) that were fed an acute high-fat diet (HFD; 45% kcal from fat) for 3 days resulted in positive energy balance and increased hepatic steatosis compared with rats that were highly aerobically fit with a high capacity for running (HCR). Here, we tested the hypothesis that poor physiological outcomes in LCR rats following acute HFD feeding are associated with alterations in cecal microbiota. LCR rats exhibited greater body weight, feeding efficiency, 3 days of ...
Source: AJP: Gastrointestinal and Liver Physiology - July 12, 2016 Category: Gastroenterology Authors: Panasevich, M. R., Morris, E. M., Chintapalli, S. V., Wankhade, U. D., Shankar, K., Britton, S. L., Koch, L. G., Thyfault, J. P., Rector, R. S. Tags: MICROBIOME AND HOST INTERACTIONS Source Type: research

Autophagy induced by exogenous bile acids is therapeutic in a model of {alpha}-1-AT deficiency liver disease
The bile acid nor-ursodeoxycholic acid (norUDCA) has many biological actions, including antiapoptotic effects. Homozygous PIZZ α-1-antitrypsin (A1AT)-deficient humans are known to be at risk for liver disease, cirrhosis, and liver cancer as a result of the accumulation of the toxic, A1AT mutant Z protein within hepatocytes. This accumulation triggers cell death in the hepatocytes with the largest mutant Z-protein burdens, followed by compensatory proliferation. Proteolysis pathways within the hepatocyte, including autophagy, act to reduce the intracellular burden of A1AT Z protein. We hypothesized that norUDCA would ...
Source: AJP: Gastrointestinal and Liver Physiology - July 12, 2016 Category: Gastroenterology Authors: Tang, Y., Fickert, P., Trauner, M., Marcus, N., Blomenkamp, K., Teckman, J. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Identification of intestinal ion transport defects in microvillus inclusion disease
Loss of function mutations in the actin motor myosin Vb (Myo5b) lead to microvillus inclusion disease (MVID) and death in newborns and children. MVID results in secretory diarrhea, brush border (BB) defects, villus atrophy, and microvillus inclusions (MVIs) in enterocytes. How loss of Myo5b results in increased stool loss of chloride (Cl–) and sodium (Na+) is unknown. The present study used Myo5b loss-of-function human MVID intestine, polarized intestinal cell models of secretory crypt (T84) and villus resembling (CaCo2BBe, C2BBe) enterocytes lacking Myo5b in conjunction with immunofluorescence confocal stimulated em...
Source: AJP: Gastrointestinal and Liver Physiology - July 12, 2016 Category: Gastroenterology Authors: Kravtsov, D. V., Ahsan, M. K., Kumari, V., van Ijzendoorn, S. C. D., Reyes-Mugica, M., Kumar, A., Gujral, T., Dudeja, P. K., Ameen, N. A. Tags: EPITHELIAL BIOLOGY AND SECRETION Source Type: research

Type 3 muscarinic receptors contribute to intestinal mucosal homeostasis and clearance of Nippostrongylus brasiliensis through induction of TH2 cytokines
Despite increased appreciation for the role of nicotinic receptors in the modulation of and response to inflammation, the contribution of muscarinic receptors to mucosal homeostasis, clearance of enteric pathogens, and modulation of immune cell function remains relatively undefined. Uninfected and Nippostrongylus brasiliensis-infected wild-type and type 3 muscarinic receptor (M3R)-deficient (Chrm3–/–) mice were studied to determine the contribution of M3R to mucosal homeostasis as well as host defense against the TH2-eliciting enteric nematode N. brasiliensis. Intestinal permeability and expression of TH1/TH17 ...
Source: AJP: Gastrointestinal and Liver Physiology - July 12, 2016 Category: Gastroenterology Authors: McLean, L. P., Smith, A., Cheung, L., Urban, J. F., Sun, R., Grinchuk, V., Desai, N., Zhao, A., Raufman, J.-P., Shea-Donohue, T. Tags: EPITHELIAL BIOLOGY AND SECRETION Source Type: research