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https://www.readbyqxmd.com/read/28630260/cholesterol-auxotrophy-and-intolerance-to-ezetimibe-in-mice-with-srebp-2-deficiency-in-the-intestine
#1
Shunxing Rong, Jeffrey McDonald, Luke Engelking
Sterol regulatory element-binding protein-2 (SREBP-2) activates transcription of all genes needed for cholesterol biosynthesis. To study SREBP-2 function in intestine, we generated a mouse model (Vil-BP2(-/-) ) in which Cre recombinase ablates SREBP-2 in intestinal epithelia. Intestines of Vil-BP2(-/-) mice had reduced expression of genes required for sterol synthesis, in vivo sterol synthesis rates, and epithelial cholesterol contents. On a cholesterol-free diet, they displayed chronic enteropathy with histological abnormalities of both villi and crypts, growth restriction, and reduced survival that was prevented by supplementation of cholesterol in the diet...
June 19, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28622386/alpha-defensin-dependent-enhancement-of-enteric-viral-infection
#2
Sarah S Wilson, Beth A Bromme, Mayumi K Holly, Mayim E Wiens, Anshu P Gounder, Youngmee Sul, Jason G Smith
The small intestinal epithelium produces numerous antimicrobial peptides and proteins, including abundant enteric α-defensins. Although they most commonly function as potent antivirals in cell culture, enteric α-defensins have also been shown to enhance some viral infections in vitro. Efforts to determine the physiologic relevance of enhanced infection have been limited by the absence of a suitable cell culture system. To address this issue, here we use primary stem cell-derived small intestinal enteroids to examine the impact of naturally secreted α-defensins on infection by the enteric mouse pathogen, mouse adenovirus 2 (MAdV-2)...
June 16, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28534432/gastrointestinal-microphysiological-systems
#3
Sarah E Blutt, James R Broughman, Winnie Zou, Xi-Lei Zeng, Umesh C Karandikar, Julie In, Nicholas C Zachos, Olga Kovbasnjuk, Mark Donowitz, Mary K Estes
Gastrointestinal diseases are a significant health care and economic burden. Prevention and treatment of these diseases have been limited by the available human biologic models. Microphysiological systems comprise organ-specific human cultures that recapitulate many structural, biological, and functional properties of the organ in smaller scale including aspects of flow, shear stress and chemical gradients. The development of intestinal microphysiological system platforms represents a critical component in improving our understanding, prevention, and treatment of gastrointestinal diseases...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28483523/effect-of-essential-amino-acids-on-enteroids-methionine-deprivation-suppresses-proliferation-and-affects-differentiation-in-enteroid-stem-cells
#4
Yuki Saito, Ken Iwatsuki, Hikaru Hanyu, Natsuki Maruyama, Eitaro Aihara, Miki Tadaishi, Makoto Shimizu, Kazuo Kobayashi-Hattori
We investigated the effects of essential amino acids on intestinal stem cell proliferation and differentiation using murine small intestinal organoids (enteroids) from the jejunum. By selectively removing individual essential amino acids from culture medium, we found that 24 h of methionine (Met) deprivation markedly suppressed cell proliferation in enteroids. This effect was rescued when enteroids cultured in Met deprivation media for 12 h were transferred to complete medium, suggesting that Met plays an important role in enteroid cell proliferation...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28467395/erratum-a-primary-human-macrophage-enteroid-co-culture-model-to-investigate-mucosal-gut-physiology-and-host-pathogen-interactions
#5
Gaelle Noel, Nicholas W Baetz, Janet F Staab, Mark Donowitz, Olga Kovbasnjuk, Marcela F Pasetti, Nicholas C Zachos
No abstract text is available yet for this article.
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28462380/cell-adhesion-molecule-cd166-alcam-functions-within-the-crypt-to-orchestrate-murine-intestinal-stem-cell-homeostasis
#6
Nicholas R Smith, Paige S Davies, Trevor G Levin, Alexandra C Gallagher, Douglas R Keene, Sidharth K Sengupta, Nikki Wieghard, Edward El Rassi, Melissa H Wong
BACKGROUND & AIMS: Intestinal epithelial homeostasis is maintained by active-cycling and slow-cycling stem cells confined within an instructive crypt-based niche. Exquisite regulating of these stem cell populations along the proliferation-to-differentiation axis maintains a homeostatic balance to prevent hyperproliferation and cancer. Although recent studies focus on how secreted ligands from mesenchymal and epithelial populations regulate intestinal stem cells (ISCs), it remains unclear what role cell adhesion plays in shaping the regulatory niche...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28390865/spdef-induces-quiescence-of-colorectal-cancer-cells-by%C3%A2-changing-the-transcriptional-targets-of-%C3%AE-catenin
#7
Yuan-Hung Lo, Taeko K Noah, Min-Shan Chen, Winnie Zou, Ester Borras, Eduardo Vilar, Noah F Shroyer
BACKGROUND & AIMS: The canonical Wnt signaling pathway activates the transcriptional activity of β-catenin. This pathway is often activated in colorectal cancer cells, but strategies to block it in tumors have not been effective. The SAM pointed domain containing ETS transcription factor (SPDEF) suppresses formation of colon tumors by unclear mechanisms. We investigated these mechanisms and the effects of SPDEF on β-catenin activity in mouse models of colorectal cancer (CRC), CRC cell lines, and mouse and human normal and cancer colonoids...
April 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28361480/human-intestinal-enteroids-new-models-to-study-gastrointestinal-virus-infections
#8
Winnie Y Zou, Sarah E Blutt, Sue E Crawford, Khalil Ettayebi, Xi-Lei Zeng, Kapil Saxena, Sasirekha Ramani, Umesh C Karandikar, Nicholas C Zachos, Mary K Estes
Human rotavirus (HRV) and human norovirus (HuNoV) infections are recognized as the most common causes of epidemic and sporadic cases of gastroenteritis worldwide. The study of these two human gastrointestinal viruses is important for understanding basic virus-host interactions and mechanisms of pathogenesis and to establish models to evaluate vaccines and treatments. Despite the introduction of live-attenuated vaccines to prevent life-threatening HRV-induced disease, the burden of HRV illness remains significant in low-income and less-industrialized countries, and small animal models or ex vivo models to study HRV infections efficiently are lacking...
March 31, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28359759/a-vesicle-trafficking-protein-%C3%AE-snap-regulates-paneth-cell-differentiation-in%C3%A2-vivo
#9
Susana Lechuga, Nayden G Naydenov, Alex Feygin, Antonio J Jimenez, Andrei I Ivanov
A soluble N-ethylmaleimide-sensitive factor-attachment protein alpha (αSNAP) is a multifunctional scaffolding protein that regulates intracellular vesicle trafficking and signaling. In cultured intestinal epithelial cells, αSNAP has been shown to be essential for cell survival, motility, and adhesion; however, its physiologic functions in the intestinal mucosa remain unknown. In the present study, we used a mouse with a spontaneous hydrocephalus with hop gait (hyh) mutation of αSNAP to examine the roles of this trafficking protein in regulating intestinal epithelial homeostasis in vivo...
May 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28347989/wrn-conditioned-media-is-sufficient-for-in-vitro-propagation-of-intestinal-organoids-from-large-farm-and-small-companion-animals
#10
Robin H Powell, Michael S Behnke
Recent years have seen significant developments in the ability to continuously propagate organoids derived from intestinal crypts. These advancements have been applied to mouse and human samples providing models for gastrointestinal tissue development and disease. We adapt these methods for the propagation of intestinal organoids (enteroids) from various large farm and small companion (LF/SC) animals, including cat, dog, cow, horse, pig, sheep and chicken. We show that LF/SC enteroids propagate and expand in L-WRN conditioned media containing signaling factors Wnt3a, R-spondin-3, and Noggin (WRN)...
May 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28345602/a-primary-human-macrophage-enteroid-co-culture-model-to-investigate-mucosal-gut-physiology-and-host-pathogen-interactions
#11
Gaelle Noel, Nicholas W Baetz, Janet F Staab, Mark Donowitz, Olga Kovbasnjuk, Marcela F Pasetti, Nicholas C Zachos
Integration of the intestinal epithelium and the mucosal immune system is critical for gut homeostasis. The intestinal epithelium is a functional barrier that secludes luminal content, senses changes in the gut microenvironment, and releases immune regulators that signal underlying immune cells. However, interactions between epithelial and innate immune cells to maintain barrier integrity and prevent infection are complex and poorly understood. We developed and characterized a primary human macrophage-enteroid co-culture model for in-depth studies of epithelial and macrophage interactions...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28288348/a-microengineered-collagen-scaffold-for-generating-a-polarized-crypt-villus-architecture-of-human-small-intestinal-epithelium
#12
Yuli Wang, Dulan B Gunasekara, Mark I Reed, Matthew DiSalvo, Scott J Bultman, Christopher E Sims, Scott T Magness, Nancy L Allbritton
The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available...
June 2017: Biomaterials
https://www.readbyqxmd.com/read/28192061/the-contributions-of-human-mini-intestines-to-the-study-of-intestinal-physiology-and-pathophysiology
#13
Huimin Yu, Nesrin M Hasan, Julie G In, Mary K Estes, Olga Kovbasnjuk, Nicholas C Zachos, Mark Donowitz
The lack of accessibility to normal and diseased human intestine and the inability to separate the different functional compartments of the intestine even when tissue could be obtained have held back the understanding of human intestinal physiology. Clevers and his associates identified intestinal stem cells and established conditions to grow "mini-intestines" ex vivo in differentiated and undifferentiated conditions. This pioneering work has made a new model of the human intestine available and has begun making contributions to the understanding of human intestinal transport in normal physiologic conditions and the pathophysiology of intestinal diseases...
February 10, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/28159868/using-primary-murine-intestinal-enteroids-to-study-dietary-tag-absorption-lipoprotein-synthesis-and-the-role-of-apoc-iii-in-the-intestine
#14
Javeed Jattan, Cayla Rodia, Diana Li, Adama Diakhate, Hongli Dong, Amy Bataille, Noah F Shroyer, Alison B Kohan
Since its initial report in 2009, the intestinal enteroid culture system has been a powerful tool used to study stem cell biology and development in the gastrointestinal tract. However, a major question is whether enteroids retain intestinal function and physiology. There have been significant contributions describing ion transport physiology of human intestinal organoid cultures, as well as physiology of gastric organoids, but critical studies on dietary fat absorption and chylomicron synthesis in primary intestinal enteroids have not been undertaken...
May 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28148261/dclk1-a-tumor-stem-cell-marker-regulates-pro-survival-signaling-and-self-renewal-of-intestinal-tumor-cells
#15
Parthasarathy Chandrakesan, Jiannan Yao, Dongfeng Qu, Randal May, Nathaniel Weygant, Yang Ge, Naushad Ali, Sripathi M Sureban, Modhi Gude, Kenneth Vega, Eddie Bannerman-Menson, Lijun Xia, Michael Bronze, Guangyu An, Courtney W Houchen
BACKGROUND: More than 80% of intestinal neoplasia is associated with the adenomatous polyposis coli (APC) mutation. Doublecortin-like kinase 1 (Dclk1), a kinase protein, is overexpressed in colorectal cancer and specifically marks tumor stem cells (TSCs) that self-renew and increased the tumor progeny in Apc (Min/+) mice. However, the role of Dclk1 expression and its contribution to regulating pro-survival signaling for tumor progression in Apc mutant cancer is poorly understood. METHODS: We analyzed DCLK1 and pro-survival signaling gene expression datasets of 329 specimens from TCGA Colon Adenocarcinoma Cancer Data...
February 1, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28137842/enteroviruses-infect-human-enteroids-and-induce-antiviral-signaling-in-a-cell-lineage-specific-manner
#16
Coyne G Drummond, Alexa M Bolock, Congrong Ma, Cliff J Luke, Misty Good, Carolyn B Coyne
Enteroviruses are among the most common viral infectious agents of humans and are primarily transmitted by the fecal-oral route. However, the events associated with enterovirus infections of the human gastrointestinal tract remain largely unknown. Here, we used stem cell-derived enteroids from human small intestines to study enterovirus infections of the intestinal epithelium. We found that enteroids were susceptible to infection by diverse enteroviruses, including echovirus 11 (E11), coxsackievirus B (CVB), and enterovirus 71 (EV71), and that contrary to an immortalized intestinal cell line, enteroids induced antiviral and inflammatory signaling pathways in response to infection in a virus-specific manner...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28109091/-effect-of-deoxycholic-acid-intervention-on-growth-of-ileum-organoids-derived-from-c57bl-6-mice
#17
Li-Hong Lou, Yue Zeng, Hui Zhou, Ying-Ying Lu, Xing-Peng Wang
OBJECTIVE: To establish a culture system for mouse intestinal organoids and investigate the effect of deoxycholic acid (DCA) on organoids growth. METHODS: The terminal ileum was collected from 8-month-old C57BL<6 mice. The tissue blocks were treated with EDTA and the crypts were collected and embedded in Matrigel Matrix. Orgnoids growth and buddings were observed in the control group, anhydrous alcohol group, short-term (2 days) 100 µmol<L DCA treatment group, and long-term (10 days) 10 µmol<L DCA treatment group; the orgnoids were further cultured for 10 days after removal of DCA from the medium and observed for orgnoids growth and buddings...
January 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28090567/the-rna-polymerase-iii-subunit-polr3b-is-required-for-the-maintenance-of-small-intestinal-crypts-in-mice
#18
Julia Kieckhaefer, Sabina Lukovac, Diana Z Ye, Dolim Lee, Danielle J Beetler, Michael Pack, Klaus H Kaestner
BACKGROUND & AIMS: The continuously self-renewing mammalian intestinal epithelium, with high cellular turnover, depends on adequate protein synthesis for its proliferative capacity. RNA polymerase III activity is closely related to cellular growth and proliferation. Here, we studied the role of Polr3b, a large RNA polymerase III subunit, in the mammalian intestinal epithelium. METHODS: We derived mice with an intestinal epithelium-specific hypomorphic mutation of the Polr3b gene, using VillinCre-mediated gene ablation...
November 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28090566/large-animal-models-the-key-to-translational-discovery-in-digestive-disease-research
#19
Amanda Ziegler, Liara Gonzalez, Anthony Blikslager
Gastrointestinal disease is a prevalent cause of morbidity and mortality and the use of animal models have been instrumental in studying mechanisms of digestive pathophysiology. As investigators attempt to translate the wealth of basic science information developed from rodent, models, large animal models provide a number of translational advantages. The pig, in particular, is arguably one of the most powerful models of human organ systems, including the gastrointestinal tract. The pig has provided important tools and insight into intestinal ischemia/reperfusion injury, intestinal mucosal repair, as well as new insights into esophageal injury and repair...
November 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28069942/a-paradox-of-transcriptional-and-functional-innate-interferon-responses-of-human-intestinal-enteroids-to-enteric-virus-infection
#20
Kapil Saxena, Lukas M Simon, Xi-Lei Zeng, Sarah E Blutt, Sue E Crawford, Narayan P Sastri, Umesh C Karandikar, Nadim J Ajami, Nicholas C Zachos, Olga Kovbasnjuk, Mark Donowitz, Margaret E Conner, Chad A Shaw, Mary K Estes
The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-α/β) and type III IFN (IFN-λ) function at the epithelial level, and their respective efficacies depend on the specific pathogen and site of infection. However, the roles of type I and type III IFN in restricting human enteric viruses are poorly characterized as a result of the difficulties in cultivating these viruses in vitro and directly obtaining control and infected small intestinal human tissue...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
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