PubMed Central (PMC3 - NLM DTD)
(2.524.943 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
American Journal of Physiology - Gastrointestinal and Liver Physiology
Mostrando recursos 1 - 20 de 592
1.
Genetic epidemiology and pharmacogenetics in irritable bowel syndrome - Camilleri, Michael; Katzka, David A.
The objectives of this review are twofold. Our first objective is to evaluate the evidence supporting a role for genetics in irritable bowel syndrome (IBS). Specific examples of the associations of genetic variation and symptoms, syndromes, and intermediate phenotypes, including neurotransmitter (serotonergic, α2-adrenergic, and cannabinoid) mechanisms, inflammatory pathways (IL-10, TNFα, GNβ3, and susceptibility loci involved in Crohn's disease), and bile acid metabolism, are explored. The second objective is to review pharmacogenetics in IBS, with the focus on cytochrome P-450 metabolism of drugs used in IBS, modulation of motor and sensory responses to serotonergic agents based on the 5-hydroxytryptamine (5-HT) transporter-linked...
2.
Enteropathogenic Escherichia coli inhibits ileal sodium-dependent bile acid transporter ASBT - Annaba, Fadi; Sarwar, Zaheer; Gill, Ravinder K.; Ghosh, Amit; Saksena, Seema; Borthakur, Alip; Hecht, Gail A.; Dudeja, Pradeep K.; Alrefai, Waddah A.
Apical sodium-dependent bile acid transporter (ASBT) is responsible for the absorption of bile acids from the intestine. A decrease in ASBT function and expression has been implicated in diarrhea associated with intestinal inflammation. Whether infection with pathogenic microorganisms such as the enteropathogenic Escherichia coli (EPEC) affect ASBT activity is not known. EPEC is a food-borne enteric pathogen that translocates bacterial effector molecules via type three secretion system (TTSS) into host cells and is a major cause of infantile diarrhea. We investigated the effects of EPEC infection on ileal ASBT function utilizing human intestinal Caco2 cells and HEK-293 cells stably transfected...
3.
Ret heterozygous mice have enhanced intestinal adaptation after massive small bowel resection - Hitch, Meredith C.; Leinicke, Jennifer A.; Wakeman, Derek; Guo, Jun; Erwin, Chris R.; Rowland, Kathryn J.; Merrick, Ellen C.; Heuckeroth, Robert O.; Warner, Brad W.
Intestinal adaptation is an important compensatory response to massive small bowel resection (SBR) and occurs because of a proliferative stimulus to crypt enterocytes by poorly understood mechanisms. Recent studies suggest the enteric nervous system (ENS) influences enterocyte proliferation. We, therefore, sought to determine whether ENS dysfunction alters resection-induced adaptation responses. Ret+/− mice with abnormal ENS function and wild-type (WT) littermates underwent sham surgery or 50% SBR. After 7 days, ileal morphology, enterocyte proliferation, apoptosis, and selected signaling proteins were characterized. Crypt depth and villus height were equivalent at baseline in WT and Ret+/− mice. In contrast after SBR, Ret+/− mice...
4.
3-D illustration of network orientations of interstitial cells of Cajal subgroups in human colon as revealed by deep-tissue imaging with optical clearing - Liu, Yuan-An; Chung, Yuan-Chiang; Pan, Shien-Tung; Hou, Yung-Chi; Peng, Shih-Jung; Pasricha, Pankaj J.; Tang, Shiue-Cheng
Morphological changes of interstitial cells of Cajal (ICC) have been proposed to characterize motility disorders. However, a global view of the network orientations of ICC subgroups has not been established to illustrate their three-dimensional (3-D) architectures in the human colon. In this research, we integrate c-kit immunostaining, 3-D microscopy with optical clearing, and image rendering to present the location-dependent network orientations with high definition. Full-depth colonic tissues were obtained from colectomies performed for nonobstructing carcinoma. Specimens of colon wall were prepared away from the tumor site. C-kit and nuclear fluorescent staining were used to identify the ICC processes and cell...
5.
P2X7 receptor-mediated purinergic signaling promotes liver injury in acetaminophen hepatotoxicity in mice - Hoque, Rafaz; Sohail, Muhammed Adnan; Salhanick, Steven; Malik, Ahsan F.; Ghani, Ayaz; Robson, Simon C.; Mehal, Wajahat Z.
Inflammation contributes to liver injury in acetaminophen (APAP) hepatotoxicity in mice and is triggered by stimulation of immune cells. The purinergic receptor P2X7 is upstream of the nod-like receptor family, pryin domain containing-3 (NLRP3) inflammasome in immune cells and is activated by ATP and NAD that serve as damage-associated molecular patterns. APAP hepatotoxicity was assessed in mice genetically deficient in P2X7, the key inflammatory receptor for nucleotides (P2X7−/−), and in wild-type mice. P2X7−/− mice had significantly decreased APAP-induced liver necrosis. In addition, APAP-poisoned mice were treated with the specific P2X7 antagonist A438079 or etheno-NAD, a competitive antagonist of NAD. Pre-...
6.
Neural and neuro-immune mechanisms of visceral hypersensitivity in irritable bowel syndrome - Feng, Bin; La, Jun Ho; Schwartz, Erica S.; Gebhart, G. F.
Irritable bowel syndrome (IBS) is characterized as functional because a pathobiological cause is not readily apparent. Considerable evidence, however, documents that sensitizing proinflammatory and lipotoxic lipids, mast cells and their products, tryptases, enteroendocrine cells, and mononuclear phagocytes and their receptors are increased in tissues of IBS patients with colorectal hypersensitivity. It is also clear from recordings in animals of the colorectal afferent innervation that afferents exhibit long-term changes in models of persistent colorectal hypersensitivity. Such changes in afferent excitability and responses to mechanical stimuli are consistent with relief of discomfort and pain in IBS patients, including relief of referred abdominal...
7.
DMT1 (IRE) expression in intestinal and erythroid cells is regulated by peripheral benzodiazepine receptor-associated protein 7 - Okazaki, Yasumasa; Ma, Yuxiang; Yeh, Mary; Yin, Hong; Li, Zhen; Yeh, Kwo-yih; Glass, Jonathan
The divalent metal transporter 1 (DMT1) is essential for cellular uptake of iron, mediating iron absorption across the duodenal brush border membrane. We have previously shown that with iron feeding DMT1 in the brush border membrane undergoes endocytosis into the subapical compartment of enterocytes. To understand the mechanisms of iron-induced endocytosis of DMT1, we used the yeast two-hybrid system to find proteins that interact with DMT1 and isolated from a rat duodenal cDNA library a protein that interacts specifically with the IRE containing isoform of DMT1 {DMT1 [iron-responsive element (IRE)]}. The protein (Genbank AY336075) is 97.5% identical with peripheral benzodiazepine...
8.
Activation of two distinct Sox9-EGFP-expressing intestinal stem cell populations during crypt regeneration after irradiation - Van Landeghem, Laurianne; Santoro, M. Agostina; Krebs, Adrienne E.; Mah, Amanda T.; Dehmer, Jeffrey J.; Gracz, Adam D.; Scull, Brooks P.; McNaughton, Kirk; Magness, Scott T.; Lund, P. Kay
Recent identification of intestinal epithelial stem cell (ISC) markers and development of ISC reporter mice permit visualization and isolation of regenerating ISCs after radiation to define their functional and molecular phenotypes. Previous studies in uninjured intestine of Sox9-EGFP reporter mice demonstrate that ISCs express low levels of Sox9-EGFP (Sox9-EGFP Low), whereas enteroendocrine cells (EEC) express high levels of Sox9-EGFP (Sox9-EGFP High). We hypothesized that Sox9-EGFP Low ISCs would expand after radiation, exhibit enhanced proliferative capacities, and adopt a distinct gene expression profile associated with rapid proliferation. Sox9-EGFP mice were given 14 Gy abdominal radiation and studied between days 3 and...
9.
Oncogenic KRAS regulates BMP4 expression in colon cancer cell lines - Duerr, Eva-Maria; Mizukami, Yusuke; Moriichi, Kentaro; Gala, Manish; Jo, Won-Seok; Kikuchi, Hirotoshi; Xavier, Ramnik J.; Chung, Daniel C.
Activating mutations in the KRAS oncogene are common in colorectal cancer. However, the complete spectrum of KRAS targets that mediate its tumorigenic effect has not yet been fully delineated. We identified bone morphogenetic protein 4 (Bmp4), a transforming growth factor-β family member that regulates development and tissue homeostasis, as a new target of KRAS. In SW480, Hela, and 293 cells, oncogenic KRASV12 downregulated BMP4 RNA levels, a BMP4 promoter luciferase construct, and Bmp4 protein levels. The MEK inhibitor PD98059 but not the phosphatidylinositol 3-kinase inhibitor LY294002 blocked this downregulation of BMP4. To identify the region of the BMP4 promoter that...
10.
L-arginine uptake by cationic amino acid transporter 2 is essential for colonic epithelial cell restitution - Singh, Kshipra; Coburn, Lori A.; Barry, Daniel P.; Boucher, Jean-Luc; Chaturvedi, Rupesh; Wilson, Keith T.
Restoration of the colonic epithelial barrier is an important response during colitis. L-arginine (L-Arg) is a semiessential amino acid that reduces murine colitis induced by Citrobacter rodentium. Cationic amino acid transporter (CAT) proteins increase L-Arg uptake into cells. L-Arg is utilized to produce nitric oxide (NO), by inducible NO synthase (iNOS), or L-ornithine (L-Orn) by arginase (Arg) enzymes. The latter is followed by generation of polyamines by ornithine decarboxylase (ODC) and L-proline (L-Pro) by ornithine aminotransferase (OAT). We show that L-Arg enhanced epithelial restitution in conditionally immortalized young adult mouse colon (YAMC) cells in a wound repair model, and in...
11.
Bile acids via FXR initiate the expression of major transporters involved in the enterohepatic circulation of bile acids in newborn mice - Cui, Julia Yue; Aleksunes, Lauren M.; Tanaka, Yuji; Fu, Zidong Donna; Guo, Ying; Guo, Grace Liejun; Lu, Hong; Zhong, Xiao-bo; Klaassen, Curtis D.
The enterohepatic circulation (EHC) of bile acids (BAs) plays a pivotal role in facilitating lipid absorption. Therefore, initiation of the EHC in newborns is of crucial importance for lipid absorption from milk. The purpose of this study was to determine at what age BA transporters in liver are expressed, and the mechanism for their initiation. Serum and liver samples were collected from C57BL/6 mice at 2 days before birth and various postnatal ages. Messenger RNA assays revealed a dramatic increase at birth in the expression of the BA transporters (Ntcp, Bsep, Mrp4, Ostβ), as well as the phospholipid floppase Mdr2...
12.
Mitochondrial DNA polymerase editing mutation, PolgD257A, disturbs stem-progenitor cell cycling in the small intestine and restricts excess fat absorption - Fox, Raymond G.; Magness, Scott; Kujoth, Gregory C.; Prolla, Tomas A.; Maeda, Nobuyo
Changes in intestinal absorption of nutrients are important aspects of the aging process. To address this issue, we investigated the impact of accelerated mitochondrial DNA mutations on the stem/progenitor cells in the crypts of Lieberkühn in mice homozygous for a mitochondrial DNA polymerase gamma mutation, PolgD257A, that exhibit accelerated aging phenotype. As early as 3–7 mo of age, the small intestine was significantly enlarged in the PolgD257A mice. The crypts of the PolgD257A mice contained 20% more cells than those of their wild-type littermates and exhibited a 10-fold increase in cellular apoptosis primarily in the stem/progenitor cell zones. Actively dividing...
13.
Colonic microbiome is altered in alcoholism - Mutlu, Ece A.; Gillevet, Patrick M.; Rangwala, Huzefa; Sikaroodi, Masoumeh; Naqvi, Ammar; Engen, Phillip A.; Kwasny, Mary; Lau, Cynthia K.; Keshavarzian, Ali
Several studies indicate the importance of colonic microbiota in metabolic and inflammatory disorders and importance of diet on microbiota composition. The effects of alcohol, one of the prominent components of diet, on colonic bacterial composition is largely unknown. Mounting evidence suggests that gut-derived bacterial endotoxins are cofactors for alcohol-induced tissue injury and organ failure like alcoholic liver disease (ALD) that only occur in a subset of alcoholics. We hypothesized that chronic alcohol consumption results in alterations of the gut microbiome in a subgroup of alcoholics, and this may be responsible for the observed inflammatory state and endotoxemia in alcoholics. Thus...
14.
Src-mediated aryl hydrocarbon and epidermal growth factor receptor cross talk stimulates colon cancer cell proliferation - Xie, Guofeng; Peng, Zhongsheng; Raufman, Jean-Pierre
The aryl hydrocarbon receptor (AhR) mediates many toxic effects of environmental pollutants. AhR also interacts with multiple growth factor-driven signaling pathways. In the course of examining effects of growth factors on proliferation of human colon cancer cells, we identified cross talk between AhR and the epidermal growth factor receptor (EGFR). In the present work, we explored underlying signal transduction mechanisms and functional consequences of this interaction. With the use of two human colon cancer cell lines, H508 and SNU-C4, we examined the effects of AhR ligands including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cell proliferation and activation of EGFR, ERK1/2, and Src kinases....
15.
Divergent fate and origin of neurosphere-like bodies from different layers of the gut - Becker, Laren; Kulkarni, Subhash; Tiwari, Gunjan; Micci, Maria-Adelaide; Pasricha, Pankaj Jay
Enteric neural stem cells (ENSCs) are a population of neural crest-derived multipotent stem cells present in postnatal gut that may play an important role in regeneration of the enteric nervous system. In most studies, these cells have been isolated from the layer of the gut containing the myenteric plexus. However, a recent report demonstrated that neurosphere-like bodies (NLBs) containing ENSCs could be isolated from mucosal biopsy specimens from children, suggesting that ENSCs are present in multiple layers of the gut. The aim of our study was to assess whether NLBs isolated from layers of gut containing either myenteric or submucosal...
16.
p38 MAPK regulates Bax activity and apoptosis in enterocytes at baseline and after intestinal resection - Wakeman, Derek; Guo, Jun; Santos, Jethrina A.; Wandu, Wambui S.; Schneider, John E.; McMellen, Mark E.; Leinicke, Jennifer A.; Erwin, Christopher R.; Warner, Brad W.
Increased apoptosis in crypt enterocytes is a key feature of intestinal adaptation following massive small bowel resection (SBR). Expression of the proapoptotic factor Bax has been shown to be required for resection-induced apoptosis. It has also been demonstrated that p38-α MAPK (p38) is necessary for Bax activation and apoptosis in vitro. The present studies were designed to test the hypothesis that p38 is a key regulator of Bax activation during adaptation after SBR in vivo. Enterocyte expression of p38 was deleted by tamoxifen administration to activate villin-Cre in adult mice with a floxed Mapk14 (p38-α) gene. Proximal 50% SBR or...
17.
Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine - Weerachayaphorn, Jittima; Mennone, Albert; Soroka, Carol J.; Harry, Kathy; Hagey, Lee R.; Kensler, Thomas W.; Boyer, James L.
The transcription factor nuclear factor-E2-related factor 2 (Nrf2) is a key regulator for induction of hepatic detoxification and antioxidant mechanisms, as well as for certain hepatobiliary transporters. To examine the role of Nrf2 in bile acid homeostasis and cholestasis, we assessed the determinants of bile secretion and bile acid synthesis and transport before and after bile duct ligation (BDL) in Nrf2−/− mice. Our findings indicate reduced rates of biliary bile acid and GSH excretion, higher levels of intrahepatic bile acids, and decreased expression of regulators of bile acid synthesis, Cyp7a1 and Cyp8b1, in Nrf2−/− compared with wild-type control mice. The...
18.
Direct methylation of FXR by Set7/9, a lysine methyltransferase, regulates the expression of FXR target genes - Balasubramaniyan, Natarajan; Ananthanarayanan, Meena; Suchy, Frederick J.
The farnesoid X receptor (FXR) is a ligand (bile acid)-dependent nuclear receptor that regulates target genes involved in every aspect of bile acid homeostasis. Upon binding of ligand, FXR recruits an array of coactivators and associated proteins, some of which have intrinsic enzymatic activity that modify histones or even components of the transcriptional complex. In this study, we show chromatin occupancy by the Set7/9 methyltransferase at the FXR response element (FXRE) and direct methylation of FXR in vivo and in vitro at lysine 206. siRNA depletion of Set7/9 in the Huh-7 liver cell line decreased endogenous mRNAs of the FXR...
19.
Preproendothelin-1 expression is negatively regulated by IFNγ during hepatic stellate cell activation - Li, Tianxia; Shi, Zengdun; Rockey, Don C.
Endothelin-1 (ET-1), a powerful vasoconstrictor peptide, is produced by activated hepatic stellate cells (HSC) and promotes cell proliferation, fibrogenesis, and contraction, the latter of which has been thought to be mechanistically linked to portal hypertension in cirrhosis. Interferon-γ (IFNγ), a Th1 cytokine produced by T cells, inhibits stellate cell proliferation, fibrogenesis, and muscle-specific gene expression. Whether IFNγ-induced inhibitory effects are linked to regulation of ET-1 expression in activated stellate cells remains unknown. Here we examined IFNγ's effects on preproET-1 mRNA expression and the signaling pathways underlying this process. We demonstrated that preproET-1 mRNA expression in HSCs was prominently increased during...
20.
TNF-α induces upregulation of EGFR expression and signaling in
human colonic myofibroblasts - Yoo, James; Perez, Citlali Ekaterina Rodriguez; Nie, Wenxian; Edwards, Robert A.; Sinnett-Smith, James; Rozengurt, Enrique
The myofibroblast has recently been identified as an important mediator of tumor
necrosis factor-α (TNF-α)-associated colitis and cancer, but the
mechanism(s) involved remains incompletely understood. Recent evidence suggests
that TNF-α is a central regulator of multiple inflammatory signaling
cascades. One important target of TNF-α may be the signaling pathway
downstream of the epidermal growth factor receptor (EGFR), which has been
associated with many human cancers. Here, we show that long-term exposure of
18Co cells, a model of human colonic myofibroblasts, with TNF-α led to a
striking increase in cell surface EGFR expression, an effect that was completely
inhibited by cycloheximide. Subsequent EGFR binding by EGF and heparin binding
(HB)-EGF was...
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