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https://www.readbyqxmd.com/read/29643333/srf-destabilizes-cellular-identity-by-suppressing-cell-type-specific-gene-expression-programs
#1
Takashi Ikeda, Takafusa Hikichi, Hisashi Miura, Hirofumi Shibata, Kanae Mitsunaga, Yosuke Yamada, Knut Woltjen, Kei Miyamoto, Ichiro Hiratani, Yasuhiro Yamada, Akitsu Hotta, Takuya Yamamoto, Keisuke Okita, Shinji Masui
Multicellular organisms consist of multiple cell types. The identity of these cells is primarily maintained by cell-type-specific gene expression programs; however, mechanisms that suppress these programs are poorly defined. Here we show that serum response factor (Srf), a transcription factor that is activated by various extracellular stimuli, can repress cell-type-specific genes and promote cellular reprogramming to pluripotency. Manipulations that decrease β-actin monomer quantity result in the nuclear accumulation of Mkl1 and the activation of Srf, which downregulate cell-type-specific genes and alter the epigenetics of regulatory regions and chromatin organization...
April 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29552620/activation-of-myofibroblast-trpa1-by-steroids-and-pirfenidone-ameliorates-fibrosis-in-experimental-crohn-s-disease
#2
Lin Hai Kurahara, Keizo Hiraishi, Yaopeng Hu, Kaori Koga, Miki Onitsuka, Mayumi Doi, Kunihiko Aoyagi, Hidetoshi Takedatsu, Daibo Kojima, Yoshitaka Fujihara, Yuwen Jian, Ryuji Inoue
Background & Aims: The transient receptor potential ankyrin 1 (TRPA1) channel is highly expressed in the intestinal lamina propria, but its contribution to gut physiology/pathophysiology is unclear. Here, we evaluated the function of myofibroblast TRPA1 channels in intestinal remodeling. Methods: An intestinal myofibroblast cell line (InMyoFibs) was stimulated by transforming growth factor-β1 to induce in vitro fibrosis. Trpa1 knockout mice were generated using the Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29524654/binary-clostridium-difficile-toxin-cdt-a-virulence-factor-disturbing-the-cytoskeleton
#3
Klaus Aktories, Panagiotis Papatheodorou, Carsten Schwan
Clostridium difficile infection causes antibiotics-associated diarrhea and pseudomembranous colitis. Major virulence factors of C. difficile are the Rho-glucosylating toxins TcdA and TcdB. In addition, many, so-called hypervirulent C. difficile strains produce the binary actin-ADP-ribosylating toxin CDT. CDT causes depolymerization of F-actin and rearrangement of the actin cytoskeleton. Thereby, many cellular functions, which depend on actin, are altered. CDT disturbs the dynamic balance between actin and microtubules in target cells...
March 7, 2018: Anaerobe
https://www.readbyqxmd.com/read/29487135/hypoxanthine-is-a-checkpoint-stress-metabolite-in-colonic-epithelial-energy-modulation-and-barrier-function
#4
J Scott Lee, Ruth X Wang, Erica E Alexeev, Jordi M Lanis, Kayla D Battista, Louise E Glover, Sean P Colgan
Intestinal epithelial cells form a selectively permeable barrier to protect colon tissues from luminal microbiota and antigens and to mediate nutrient, fluid, and waste flux in the intestinal tract. Dysregulation of the epithelial cell barrier coincides with profound shifts in metabolic energy, especially in the colon, which exists in an energetically depleting state of physiological hypoxia. However, studies that systematically examine energy flux and adenylate metabolism during intestinal epithelial barrier development and restoration after disruption are lacking...
April 20, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29466999/a-probiotic-complex-rosavin-zinc-and-prebiotics-ameliorate-intestinal-inflammation-in-an-acute-colitis-mouse-model
#5
Jin-Sil Park, JeongWon Choi, Ji Ye Kwon, Kyung-Ah Jung, Chul Woo Yang, Sung-Hwan Park, Mi-La Cho
BACKGROUND: An altered gut microbiota balance is involved in the pathogenesis of inflammatory bowel disease (IBD), and several probiotic strains are used as dietary supplements to improve intestinal health. We evaluated the therapeutic effect of 12 probiotics in combination with prebiotics, rosavin, and zinc in the dextran sodium sulfate (DSS)-induced colitis mouse model. METHODS: The probiotic complex or the combination drug was administered orally to mice with DSS-induced colitis, and the body weight, disease activity index, colon length, and histopathological parameters were evaluated...
February 21, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29336663/lactobacillus-acidophilus-improves-intestinal-inflammation-in-an-acute-colitis-mouse-model-by-regulation-of-th17-and-treg-cell-balance-and-fibrosis-development
#6
Jin-Sil Park, Jeong Won Choi, JooYeon Jhun, Ji Ye Kwon, Bo-In Lee, Chul Woo Yang, Sung-Hwan Park, Mi-La Cho
Disruption of the balance among the microbiota, epithelial cells, and resident immune cells in the intestine is involved in the pathogenesis of inflammatory bowel disease (IBD). Probiotics exert protective effects against IBD, and probiotic commensal Lactobacillus species are common inhabitants of the natural microbiota, especially in the gut. To investigate the effects of Lactobacillus acidophilus on the development of IBD, L. acidophilus was administered orally in mice with dextran sodium sulfate (DSS)-induced colitis...
March 2018: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29276753/indian-hedgehog-suppresses-a-stromal-cell-driven-intestinal-immune-response
#7
B Florien Westendorp, Nikè V J A Büller, Olga N Karpus, Willemijn A van Dop, Jan Koster, Rogier Versteeg, Pim J Koelink, Clinton Y Snel, Sander Meisner, Joris J T H Roelofs, Anja Uhmann, Emiel Ver Loren van Themaat, Jarom Heijmans, Heidi Hahn, Vanesa Muncan, Manon E Wildenberg, Gijs R van den Brink
Background & Aims: Upon intestinal epithelial damage a complex wound healing response is initiated to restore epithelial integrity and defend against pathogenic invasion. Epithelium-derived Indian Hedgehog (Ihh) functions as a critical sensor in this process. Signaling occurs in a paracrine manner because the receptor for Ihh is expressed only in the mesenchyme, but the exact Hedgehog target cell has remained elusive. The aim of this study was to elucidate further the nature of this target cell in the context of intestinal inflammation...
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28839442/gut-barrier-failure-biomarkers-are-associated-with-poor-disease-outcome-in-patients-with-primary-sclerosing-cholangitis
#8
Tamas Tornai, Eszter Palyu, Zsuzsanna Vitalis, Istvan Tornai, David Tornai, Peter Antal-Szalmas, Gary L Norman, Zakera Shums, Gabor Veres, Antal Dezsofi, Gabriella Par, Alajos Par, Peter Orosz, Ferenc Szalay, Peter Laszlo Lakatos, Maria Papp
AIM: To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis (PSC) patients. METHODS: Sera of 67 PSC patients [median age (range): 32 (5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin (AAA IgA/IgG) and gliadin (AGA IgA/IgG)] and for serum level of intestinal fatty acid-binding protein (I-FABP) by ELISA...
August 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28815354/nf-e2-related-factor-2-suppresses-intestinal-fibrosis-by-inhibiting-reactive-oxygen-species-dependent-tgf-%C3%AE-1-smads-pathway
#9
Yadi Guan, Yue Tan, Weiyu Liu, Jun Yang, Dongxu Wang, Di Pan, Yan Sun, Changqing Zheng
BACKGROUND AND AIMS: This study aimed to evaluate the antifibrotic effects of NF-E2-Related Factor 2 (Nrf2) on intestinal fibrosis. Intestinal fibrosis is a common complication of Crohn's disease; however, its mechanism of intestinal fibrosis is largely unclear. METHODS: BALB/c mice received 2,4,6-trinitrobenzene sulfonic acid weekly via intrarectal injections to induce chronic fibrotic colitis. They also diet containing received 1% (w/w) tert-butylhydroquinone (tBHQ), which is an agonist of Nrf2...
February 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28657883/clostridium-difficile-toxin-biology
#10
Klaus Aktories, Carsten Schwan, Thomas Jank
Clostridium difficile is the cause of antibiotics-associated diarrhea and pseudomembranous colitis. The pathogen produces three protein toxins: C. difficile toxins A (TcdA) and B (TcdB), and C. difficile transferase toxin (CDT). The single-chain toxins TcdA and TcdB are the main virulence factors. They bind to cell membrane receptors and are internalized. The N-terminal glucosyltransferase and autoprotease domains of the toxins translocate from low-pH endosomes into the cytosol. After activation by inositol hexakisphosphate (InsP6), the autoprotease cleaves and releases the glucosyltransferase domain into the cytosol, where GTP-binding proteins of the Rho/Ras family are mono-O-glucosylated and, thereby, inactivated...
September 8, 2017: Annual Review of Microbiology
https://www.readbyqxmd.com/read/28592228/anti-fibrogenic-effect-of-ppar-%C3%AE-agonists-in-human-intestinal-myofibroblasts
#11
Jun Bon Koo, Myeong-Ok Nam, Younshin Jung, Jongman Yoo, Duk Hwan Kim, Gwangil Kim, Sung Jae Shin, Kee Myung Lee, Ki Baik Hahm, Jong Woo Kim, Sung Pyo Hong, Kwang Jae Lee, Jun Hwan Yoo
BACKGROUND: Intestinal fibrosis is a serious complication of inflammatory bowel disease, including Crohn's disease and ulcerative colitis. There is no specific treatment for intestinal fibrosis. Studies have indicated that peroxisome proliferator-activated receptor- γ (PPAR-γ) agonists have anti-fibrogenic properties in organs besides the gut; however, their effects on human intestinal fibrosis are poorly understood. This study investigated the anti-fibrogenic properties and mechanisms of PPAR-γ agonists on human primary intestinal myofibroblasts (HIFs)...
June 7, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28541346/acf7-regulates-inflammatory-colitis-and-intestinal-wound-response-by-orchestrating-tight-junction-dynamics
#12
Yanlei Ma, Jiping Yue, Yao Zhang, Chenzhang Shi, Matt Odenwald, Wenguang G Liang, Qing Wei, Ajay Goel, Xuewen Gou, Jamie Zhang, Shao-Yu Chen, Wei-Jen Tang, Jerrold R Turner, Feng Yang, Hong Liang, Huanlong Qin, Xiaoyang Wu
In the intestinal epithelium, the aberrant regulation of cell/cell junctions leads to intestinal barrier defects, which may promote the onset and enhance the severity of inflammatory bowel disease (IBD). However, it remains unclear how the coordinated behaviour of cytoskeletal network may contribute to cell junctional dynamics. In this report, we identified ACF7, a crosslinker of microtubules and F-actin, as an essential player in this process. Loss of ACF7 leads to aberrant microtubule organization, tight junction stabilization and impaired wound closure in vitro...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28493993/mechanism-of-down-regulation-of-na-h-exchanger-2-in-experimental-colitis
#13
Amal Ali Soleiman, Farook Thameem, Islam Khan
BACKGROUND: The Na-H exchanger [NHE] performs an electroneutral uptake of NaCl and water from the lumen of the gastrointestinal tract. There are several distinct NHE isoforms, some of which show an altered expression in the inflammatory bowel diseases (IBD). In this study, we examined a role of NHE-2 in experimental colitis. METHODS: Colitis was induced in male Sprague-Dawley rats by intra-rectal administration of trinitrobenzenesulphonic acid (TNBS). On day 6 post-TNBS, the animals were sacrificed, colonic and ileal segments were taken out, cleaned with phosphate buffered saline and used in this study...
2017: PloS One
https://www.readbyqxmd.com/read/28432022/a-crosstalk-between-muscarinic-and-crf2-receptors-regulates-cellular-adhesion-properties-of-human-colon-cancer-cells
#14
M Pelissier-Rota, N T Chartier, B Bonaz, M R Jacquier-Sarlin
Patients with inflammatory bowel disease often suffer from chronic and relapsing intestinal inflammation that favor the development of colitis associated cancer. An alteration of the epithelial intestinal barrier function observed in IBD is supposed to be a consequence of stress. It has been proposed that corticotrophin-releasing factor receptor (CRF2), one of the two receptors of CRF, the principal neuromediator of stress, acts on cholinergic nerves to induce stress-mediated epithelial barrier dysfunction...
July 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28288330/the-pharmacodynamic-active-components-study-of-tibetan-medicine-gentianopsis-paludosa-on-ulcerative-colitis-fibrosis
#15
Nian-Hua Lu, Hui-Qiao Zhao, Ming Jing, Xiong Liu, Chun-Zhen Ren, Xue-Feng Liu, Juan-Juan Liu, Yan-Xia Zhang
The current study focused on the pharmacodynamic activity components of Gentianopsis paludosa against ulcerative colitis (UC) fibrosis including symptoms of intestinal diarrhea and inflammatory. Trinitro-benzene-sulfonic acid induced UC model rats were gavaged with gradient polarity extracts respectively from ethanol-extract of Gentianopsis paludosa. Masson staining and qRT-PCR methods were respectively used to assess the degree of UC fibrosis and detect the mRNA expressions of collagen I, collagen III, a-smooth muscle actin (α-SMA) and E-cadherin in colon tissue...
May 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28186172/appropriateness-of-reference-genes-for-normalizing-messenger-rna-in-mouse-2-4-dinitrobenzene-sulfonic-acid-dnbs-induced-colitis-using-quantitative-real-time-pcr
#16
Nour Eissa, Laëtitia Kermarrec, Hayam Hussein, Charles N Bernstein, Jean-Eric Ghia
2,4-Dinitrobenzene sulfonic acid (DNBS)-induced colitis is an experimental model that mimics Crohn's disease. Appropriateness of reference genes is crucial for RT-qPCR. This is the first study to determine the stability of reference gene expression (RGE) in mice treated with DNBS. DNBS experimental Colitis was induced in male C57BL/6 mice. RNA was extracted from colon tissue and comprehensive analysis of 13 RGE was performed according to predefined criteria. Relative colonic TNF-α and IL-1β mRNA levels were calculated...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28150820/astragaloside-iv-ameliorates-2-4-6-trinitrobenzene-sulfonic-acid-tnbs-induced-colitis-implicating-regulation-of-energy-metabolism
#17
Xu-Guang Jiang, Kai Sun, Yu-Ying Liu, Li Yan, Ming-Xia Wang, Jing-Yu Fan, Hong-Na Mu, Chong Li, Yuan-Yuan Chen, Chuan-She Wang, Jing-Yan Han
Dysfunction of energy metabolism is involved in inflammatory bowel disease (IBD). This study was designed to investigate the potential of astragaloside IV (ASIV), an active ingredient of Radix Astragalus, to ameliorate colonic mucosal injury, with focusing on the implication of energy restoration in the underlying mechanism. Experimental colitis model was established in rats by injecting 2,4,6-trinitrobenzene sulfonic acid (TNBS) through anus. After 24 hours, ASIV was administrated once daily by gavage for 6 days...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28126902/the-monomeric-gtpase-rab35-regulates-phagocytic-cup-formation-and-phagosomal-maturation-in-entamoeba-histolytica
#18
Kuldeep Verma, Sunando Datta
One of the hallmarks of amoebic colitis is the detection of Entamoeba histolytica (Eh) trophozoites with ingested erythrocytes. Therefore, erythrophagocytosis is traditionally considered as one of the most important criteria to identify the pathogenic behavior of the amoebic trophozoites. Phagocytosis is an essential process for the proliferation and virulence of this parasite. Phagocytic cargo, upon internalization, follows a defined trafficking route to amoebic lysosomal degradation machinery. Here, we demonstrated the role of EhRab35 in the early and late phases of erythrophagocytosis by the amoeba...
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28120846/cortactin-deficiency-causes-increased-rhoa-rock1-dependent-actomyosin-contractility-intestinal-epithelial-barrier-dysfunction-and-disproportionately-severe-dss-induced-colitis
#19
A F Citalán-Madrid, H Vargas-Robles, A García-Ponce, M Shibayama, A Betanzos, P Nava, C Salinas-Lara, K Rottner, R Mennigen, M Schnoor
The intestinal epithelium constitutes a first line of defense of the innate immune system. Epithelial dysfunction is a hallmark of intestinal disorders such as inflammatory bowel diseases (IBDs). The actin cytoskeleton controls epithelial barrier integrity but the function of actin regulators such as cortactin is poorly understood. Given that cortactin controls endothelial permeability, we hypothesized that cortactin is also important for epithelial barrier regulation. We found increased permeability in the colon of cortactin-KO mice that was accompanied by reduced levels of ZO-1, claudin-1, and E-cadherin...
September 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/27881401/alterations-of-colonic-function-in-the-winnie-mouse-model-of-spontaneous-chronic-colitis
#20
Ainsley M Robinson, Ahmed A Rahman, Simona E Carbone, Sarron Randall-Demllo, Rhiannon Filippone, Joel C Bornstein, Rajaraman Eri, Kulmira Nurgali
The Winnie mouse, carrying a missense mutation in Muc2, is a model for chronic intestinal inflammation demonstrating symptoms closely resembling inflammatory bowel disease (IBD). Alterations to the immune environment, morphological structure, and innervation of Winnie mouse colon have been identified; however, analyses of intestinal transit and colonic functions have not been conducted. In this study, we investigated in vivo intestinal transit in radiographic studies and in vitro motility of the isolated colon in organ bath experiments...
January 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
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