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https://www.readbyqxmd.com/read/29133078/enteric-delivery-of-regenerating-family-member-3-alpha-alters-the-intestinal-microbiota-and-controls-inflammation-in-mice-with-colitis
#1
Marion Darnaud, Alexandre Dos Santos, Patrick Gonzalez, Sandrine Augui, Claire Lacoste, Christophe Desterke, Gert De Hertogh, Emma Valentino, Emilie Braun, Jinzi Zheng, Raphael Boisgard, Christel Neut, Laurent Dubuquoy, Franck Chiappini, Didier Samuel, Patricia Lepage, Francesca Guerrieri, Joel Doré, Christian Bréchot, Nicolas Moniaux, Jamila Faivre
BACKGROUND & AIMS: Paneth cell dysfunction causes deficiencies in intestinal C-type lectins and antimicrobial peptides, which leads to dysbiosis of the intestinal microbiota, alters the mucosal barrier, and promotes development of inflammatory bowel diseases. We investigated whether transgenic expression of the human regenerating family member 3 alpha gene (REG3A) alters the fecal microbiota and affects development of colitis in mice. METHODS: We performed studies with C57BL/6 mice that express human regenerating family member 3 alpha (hREG3A) in hepatocytes, via the albumin gene promoter...
November 10, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29040430/transcriptomic-landscape-of-treatment-na%C3%A3-ve-ulcerative-colitis
#2
Hagar Taman, Christopher G Fenton, Inga V Hensel, Endre Anderssen, Jon Florholmen, Ruth H Paulssen
Background and Aims: Ulcerative colitis (UC) is a chronic inflammatory disease that effects the gastrointestinal tract and is considered one of the most prominent and common forms of inflammatory bowel disease (IBD). This study aimed to define and describe the entire transcriptomic landscape in a well-stratified, treatment-naïve UC patient population compared to control patients by using next-generation technology, RNA-Seq. Methods: Mucosal biopsies from treatment-naïve UC patients (n=14), and healthy controls (n=16) underwent RNA-Seq...
October 10, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28945764/high-incidence-of-extensive-chronic-graft-versus-host-disease-in-patients-with-the-reg3a-rs7588571-non-gg-genotype
#3
Daisuke Koyama, Makoto Murata, Ryo Hanajiri, Shingo Okuno, Sonoko Kamoshita, Jakrawadee Julamanee, Erina Takagi, Daiki Hirano, Kotaro Miyao, Reona Sakemura, Tatsunori Goto, Fumihiko Hayakawa, Aika Seto, Yukiyasu Ozawa, Koichi Miyamura, Seitaro Terakura, Tetsuya Nishida, Hitoshi Kiyoi
Regenerating islet-derived protein 3 alpha (REG3A) is a biomarker of lower gastrointestinal graft-versus-host disease (GVHD); however, the biological role of REG3A in the pathophysiology of GVHD is not understood. Here, we examined the association between a single nucleotide polymorphism in the REG3A gene, rs7588571, which is located upstream and within 2 kb of the REG3A gene, and transplant outcomes including the incidence of GVHD. The study population consisted of 126 adult Japanese patients who had undergone bone marrow transplantation from a HLA-matched sibling...
2017: PloS One
https://www.readbyqxmd.com/read/28877242/comparative-quantitative-proteomic-analysis-of-disease-stratified-laser-captured-microdissected-human-islets-identifies-proteins-and-pathways-potentially-related-to-type-1-diabetes
#4
Julius O Nyalwidhe, Wojciech J Grzesik, Tanya C Burch, Michele L Semeraro, Tayab Waseem, Ivan C Gerling, Raghavendra G Mirmira, Margaret A Morris, Jerry L Nadler
Type 1 diabetes (T1D) is a chronic inflammatory disease that is characterized by autoimmune destruction of insulin-producing pancreatic beta cells. The goal of this study was to identify novel protein signatures that distinguish Islets from patients with T1D, patients who are autoantibody positive without symptoms of diabetes, and from individuals with no evidence of disease. High resolution high mass accuracy label free quantitative mass spectrometry analysis was applied to islets isolated by laser capture microdissection from disease stratified human pancreata from the Network for Pancreatic Organ Donors with Diabetes (nPOD), these included donors without diabetes, donors with T1D-associated autoantibodies in the absence of diabetes, and donors with T1D...
2017: PloS One
https://www.readbyqxmd.com/read/28774595/il-36%C3%AE-induced-by-the-tlr3-slug-vdr-axis-promotes-wound-healing-via-reg3a
#5
Ziwei Jiang, Yuanqi Liu, Changwei Li, Leilei Chang, Wang Wang, Zhenhua Wang, Xiaoguang Gao, Bernhard Ryffel, Yelin Wu, Yuping Lai
IL-36 family members are highly expressed in hyperproliferative keratinocytes and play an important role in the pathogenesis of skin diseases such as psoriasis. However, whether and how IL-36 cytokines are induced to promote wound healing remains unknown. Here we showed that skin injury increased the expression of IL-36γ to promote wound healing. Mechanistically, the expression of IL-36γ was induced by RNAs from damaged cells via the activation of toll-like receptor 3 (TLR3) and TIR-domain-containing adapter-inducing IFN-β (TRIF) followed by the induction of a zinc finger protein SLUG to abrogate the inhibitory effect of vitamin D receptor (VDR) on the promoter of IL-36γ gene...
July 31, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28656348/pap-reg3a-favors-perineural-invasion-in-pancreatic-adenocarcinoma-and-serves-as-a-prognostic-marker
#6
Jérémy Nigri, Meritxell Gironella, Christian Bressy, Elena Vila-Navarro, Julie Roques, Sophie Lac, Caroline Bontemps, Coraline Kozaczyk, Jérôme Cros, Daniel Pietrasz, Raphaël Maréchal, Jean-Luc Van Laethem, Juan Iovanna, Jean-Baptiste Bachet, Emma Folch-Puy, Richard Tomasini
Pancreatic ductal adenocarcinoma (PDA) is a fatal and insidious malignant disease for which clinicians' tools are restricted by the current limits in knowledge of how tumor and stromal cells act during the disease. Among PDA hallmarks, neural remodeling (NR) and perineural invasion (PNI) drastically influence quality of life and patient survival. Indeed, NR and PNI are associated with neuropathic pain and metastasis, respectively, both of which impact clinicians' decisions and therapeutic options. The aim of this study was to determine the impact and clinical relevance of the peritumoral microenvironment, through pancreatitis-associated protein (PAP/REG3A) expression, on PNI in pancreatic cancer...
November 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28435292/reg3a-promotes-the-proliferation-migration-and-invasion-of-gastric-cancer-cells
#7
Zhou-Feng Chen, Zhi-Ming Huang, Hai-Bo Xue, Xiu-Qing Lin, Ren-Ping Chen, Meng-Jun Chen, Rui-Fang Jin
The mechanism underlying the metastasis of gastric cancer (GC) cells remains elusive. REG3A is considered an oncogene in various cancers, but in GC its role is unclear. Here, we report that the expression of REG3A was significantly increased in the tumor tissues of patients with GC compared with the matched normal tissues. Knockdown of REG3A induced by specific small interfering RNA (siRNA) significantly repressed the proliferation of GC cells for 24 h or 48 h. Moreover, knockdown of REG3A significantly suppressed the migration, invasion, and adhesion of GC cells in vitro...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27846243/bacterially-associated-transcriptional-remodelling-in-a-distinct-genomic-subtype-of-colorectal-cancer-provides-a-plausible-molecular-basis-for-disease-development
#8
Katie S Lennard, Ryan W Goosen, Jonathan M Blackburn
The relevance of specific microbial colonisation to colorectal cancer (CRC) disease pathogenesis is increasingly recognised, but our understanding of possible underlying molecular mechanisms that may link colonisation to disease in vivo remains limited. Here, we investigate the relationships between the most commonly studied CRC-associated bacteria (Enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, Fusobacterium spp., afaC+ E. coli, Enterococcus faecalis & Enteropathogenic E. coli) and altered transcriptomic and methylation profiles of CRC patients, in order to gain insight into the potential contribution of these bacteria in the aetiopathogenesis of CRC...
2016: PloS One
https://www.readbyqxmd.com/read/27830702/hyperglycaemia-inhibits-reg3a-expression-to-exacerbate-tlr3-mediated-skin-inflammation-in-diabetes
#9
Yelin Wu, Yanchun Quan, Yuanqi Liu, Keiwei Liu, Hongquan Li, Ziwei Jiang, Tian Zhang, Hu Lei, Katherine A Radek, Dongqing Li, Zhenhua Wang, Jilong Lu, Wang Wang, Shizhao Ji, Zhaofan Xia, Yuping Lai
Dysregulated inflammatory responses are known to impair wound healing in diabetes, but the underlying mechanisms are poorly understood. Here we show that the antimicrobial protein REG3A controls TLR3-mediated inflammation after skin injury. This control is mediated by REG3A-induced SHP-1 protein, and acts selectively on TLR3-activated JNK2. In diabetic mouse skin, hyperglycaemia inhibits the expression of IL-17-induced IL-33 via glucose glycation. The decrease in cutaneous IL-33 reduces REG3A expression in epidermal keratinocytes...
November 10, 2016: Nature Communications
https://www.readbyqxmd.com/read/27788482/reg-proteins-promote-acinar-to-ductal-metaplasia-and-act-as-novel-diagnostic-and-prognostic-markers-in-pancreatic-ductal-adenocarcinoma
#10
Qing Li, Hao Wang, George Zogopoulos, Qin Shao, Kun Dong, Fudong Lv, Karam Nwilati, Xian-Yong Gui, Adeline Cuggia, Jun-Li Liu, Zu-Hua Gao
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor. Acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) are both precursor lesions that lead to the development of PDAC. Reg family proteins (Reg1A, 1B, 3A/G, 4) are a group of calcium-dependent lectins that promote islet growth in response to inflammation and/or injuries. The aim of this study was to establish a role for Reg proteins in the development of PDAC and their clinical value as biomarkers. We found that Reg1A and Reg3A/G were highly expressed in the ADM tissues by immunohistochemistry...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27693023/a-single-cell-transcriptome-atlas-of-the-human-pancreas
#11
Mauro J Muraro, Gitanjali Dharmadhikari, Dominic Grün, Nathalie Groen, Tim Dielen, Erik Jansen, Leon van Gurp, Marten A Engelse, Francoise Carlotti, Eelco J P de Koning, Alexander van Oudenaarden
To understand organ function, it is important to have an inventory of its cell types and of their corresponding marker genes. This is a particularly challenging task for human tissues like the pancreas, because reliable markers are limited. Hence, transcriptome-wide studies are typically done on pooled islets of Langerhans, obscuring contributions from rare cell types and of potential subpopulations. To overcome this challenge, we developed an automated platform that uses FACS, robotics, and the CEL-Seq2 protocol to obtain the transcriptomes of thousands of single pancreatic cells from deceased organ donors, allowing in silico purification of all main pancreatic cell types...
October 26, 2016: Cell Systems
https://www.readbyqxmd.com/read/26646797/up-regulation-of-reg3a-in-colorectal-cancer-cells-confers-proliferation-and-correlates-with-colorectal-cancer-risk
#12
Ying Ye, Ling Xiao, Su-Juan Wang, Wei Yue, Qiao-Shan Yin, Meng-Yao Sun, Wei Xia, Zhi-Yi Shao, Hong Zhang
Colorectal cancer (CRC) is one of the most common malignancies in the world. Previous studies have investigated the altered expression of regenerating islet-derived 3 alpha (REG3A) in various cancers. We aimed at exploring the biological function and the underlying molecular mechanism of REG3A in CRC. In this study, REG3A was found elevated in CRC compared with normal tissues. Further, high REG3A expression level was correlated with bigger tumor size, poorer differentiation, higher tumor stage and lower survival rate...
January 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/26180210/mrnas-and-protein-synthetic-machinery-localize-into-regenerating-spinal-cord-axons-when-they-are-provided-a-substrate-that-supports-growth
#13
Ashley L Kalinski, Rahul Sachdeva, Cynthia Gomes, Seung Joon Lee, Zalak Shah, John D Houle, Jeffery L Twiss
UNLABELLED: Although intra-axonal protein synthesis is well recognized in cultured neurons and during development in vivo, there have been few reports of mRNA localization and/or intra-axonal translation in mature CNS axons. Indeed, previous work indicated that mature CNS axons contain much lower quantities of translational machinery than PNS axons, leading to the conclusion that the capacity for intra-axonal protein synthesis is linked to the intrinsic capacity of a neuron for regeneration, with mature CNS neurons showing much less growth after injury than PNS neurons...
July 15, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/25779676/reg3a-accelerates-pancreatic-cancer-cell-growth-under-il-6-associated-inflammatory-condition-involvement-of-a-reg3a-jak2-stat3-positive-feedback-loop
#14
Xiulan Liu, Jun Wang, Hongjie Wang, Guoxiao Yin, Yang Liu, Xiang Lei, Ming Xiang
Regenerating gene protein (REG) 3A is a 19 kD secretory pancreas protein with pro-growth function. Previously we demonstrated that overexpression of REG3A, acting as a key molecule for up-regulation of the JAK2/STAT3 pathway, contributed to inflammation-related pancreatic cancer (PaC) development. However the exact network associated with REG3A signaling still remains unclear. Here we determined that exposure of human PaC cells to cytokine IL-6 activated the oncogenic JAK2/STAT3 pathway, which directly upregulated REG3A expression, accelerated cell cycle progression by promoting CyclinD1 expression, and enhancing the expression of the anti-apoptosis Bcl family...
June 28, 2015: Cancer Letters
https://www.readbyqxmd.com/read/25777289/obesity-exacerbates-imiquimod-induced-psoriasis-like-epidermal-hyperplasia-and-interleukin-17-and-interleukin-22-production-in-mice
#15
Kaori Kanemaru, Ayano Matsuyuki, Yoshikazu Nakamura, Kiyoko Fukami
Psoriasis is a chronic inflammatory skin disorder that is accompanied by an imbalance between the proliferation and differentiation of keratinocytes. A number of studies have suggested an association between obesity and severe psoriasis; however, it remains to be clarified whether obesity exacerbates psoriasis. To address this unsolved question, we induced psoriasiform dermatitis in mouse models for obesity. We found that obesity exaggerated the severity of psoriasiform dermatitis induced by topical application of the Toll-like receptor (TLR) 7 agonist, imiquimod...
June 2015: Experimental Dermatology
https://www.readbyqxmd.com/read/25687870/overexpression-of-plasminogen-activator-inhibitor-1-in-advanced-gastric-cancer-with-aggressive-lymph-node-metastasis
#16
Yun-Suhk Suh, Jieun Yu, Byung Chul Kim, Boram Choi, Tae-Su Han, Hye Seong Ahn, Seong-Ho Kong, Hyuk-Joon Lee, Woo Ho Kim, Han-Kwang Yang
PURPOSE: The purpose of this study is to investigate differentially expressed genes using DNA microarray between advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasis and that with a more advanced tumor stage but without LN metastasis. MATERIALS AND METHODS: Five sample pairs of gastric cancer tissue and normal gastric mucosa were taken from three patients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNA microarray experiments were analyzed, and candidate genes were identified using a volcano plot that showed ≥ 2-fold differential expression and were significant by Welch's t test (p < 0...
October 2015: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/24996521/socs3-methylation-in-synergy-with-reg3a-overexpression-promotes-cell-growth-in-pancreatic-cancer
#17
Jun Wang, Hong Zhou, Yong Han, Xiulan Liu, Min Wang, Xin Wang, Guoxiao Yin, Xu Li, Ming Xiang
UNLABELLED: Pancreatic cancer (PaC) is the fifth leading cause of cancer death in the world, but the molecular mechanisms for its development remain unclear. Regenerating islet-derived protein 3-alpha (Reg3A) has been reported overexpressed in pancreatic inflammation and associated with PaC malignancies, thus believed as a potential target in inflammation-linked pancreatic carcinogenesis. Silencing of suppressor of cytokine signaling SOCS3, a well-known feedback inhibitor of cell proliferation, has been found in many human cancers...
December 2014: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/24938522/serum-ca19-9-is-significantly-upregulated-up-to-2-years-before-diagnosis-with-pancreatic-cancer-implications-for-early-disease-detection
#18
Darragh P O'Brien, Neomal S Sandanayake, Claire Jenkinson, Aleksandra Gentry-Maharaj, Sophia Apostolidou, Evangelia-Ourania Fourkala, Stephane Camuzeaux, Oleg Blyuss, Richard Gunu, Anne Dawnay, Alexey Zaikin, Ross C Smith, Ian J Jacobs, Usha Menon, Eithne Costello, Stephen P Pereira, John F Timms
PURPOSE: Biomarkers for the early detection of pancreatic cancer are urgently needed. The primary objective of this study was to evaluate whether increased levels of serum CA19-9, CA125, CEACAM1, and REG3A are present before clinical presentation of pancreatic cancer and to assess the performance of combined markers for early detection and prognosis. EXPERIMENTAL DESIGN: This nested case-control study within the UKCTOCS included 118 single and 143 serial serum samples from 154 postmenopausal women who were subsequently diagnosed with pancreatic cancer and 304 matched noncancer controls...
February 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/24465846/microarray-analysis-of-rat-pancreas-reveals-altered-expression-of-alox15-and-regenerating-islet-derived-genes-in-response-to-iron-deficiency-and-overload
#19
Richard Coffey, Hyeyoung Nam, Mitchell D Knutson
It is well known that iron overload can result in pancreatic iron deposition, beta-cell destruction, and diabetes in humans. Recent studies in animals have extended the link between iron status and pancreatic function by showing that iron depletion confers protection against beta-cell dysfunction and diabetes. The aim of the present study was to identify genes in the pancreas that are differentially expressed in response to iron deficiency or overload. Weanling male Sprague-Dawley rats (n = 6/group) were fed iron-deficient, iron-adequate, or iron-overloaded diets for 3 weeks to alter their iron status...
2014: PloS One
https://www.readbyqxmd.com/read/24342613/hes1-promotes-the-il-22-mediated-antimicrobial-response-by-enhancing-stat3-dependent-transcription-in-human-intestinal-epithelial-cells
#20
Tatsuro Murano, Ryuichi Okamoto, Go Ito, Toru Nakata, Shuji Hibiya, Hiromichi Shimizu, Satoru Fujii, Yoshihito Kano, Tomohiro Mizutani, Shiro Yui, Junko Akiyama-Morio, Yasuhiro Nemoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Mamoru Watanabe
Notch signaling plays an essential role in the proliferation and differentiation of intestinal epithelial cells (IECs). We have previously shown that Notch signaling is up-regulated in the inflamed mucosa of ulcerative colitis (UC) and thereby plays an indispensable role in tissue regeneration. Here we show that in addition to Notch signaling, STAT3 signaling is highly activated in the inflamed mucosa of UC. Forced expression of the Notch target gene Hes1 dramatically enhanced the IL-22-mediated STAT3-dependent transcription in human IECs...
January 17, 2014: Biochemical and Biophysical Research Communications
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