Claudin-1, a Double-Edged Sword in Cancer
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A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Gene Expression Is Related to Parental Origin and Regional Coordinate Control
Journal of Human Genetics (2009) 54, 193–198 & 2009 The Japan Society of Human Genetics All rights reserved 1434-5161/09 $32.00 www.nature.com/jhg ORIGINAL ARTICLE William’s syndrome: gene expression is related to parental origin and regional coordinate control Jeremy C Collette1, Xiao-Ning Chen1, Debra L Mills2, Albert M Galaburda3, Allan L Reiss4, Ursula Bellugi5 and Julie R Korenberg1,6 William’s syndrome (WS) features a spectrum of neurocognitive and behavioral abnormalities due to a rare 1.5 MB deletion that includes about 24–28 genes on chromosome band 7q11.23. Study of the expression of these genes from the single normal copy provides an opportunity to elucidate the genetic and epigenetic controls on these genes as well as their roles in both WS and normal brain development and function. We used quantitative RT-PCR to determine the transcriptional level of 14 WS gene markers in a cohort of 77 persons with WS and 48 normal controls. Results reported here: (1) show that the expression of the genes deleted in WS is decreased in some but not all cases, (2) demonstrate that the parental origin of the deletion contributes to the level of expression of GTF2I independently of age and gender and (3) indicate that the correlation of expression between GTF2I and some other genes in the WS region differs in WS subjects and normal controls, which in turn points toward a regulatory role for this gene. Interspecies comparisons suggest GTF2I may play a key role in normal brain development. Journal of Human Genetics (2009) 54, 193–198; doi:10.1038/jhg.2009.5; published online 13 March 2009 Keywords: William’s syndrome; gene expression; RT-PCR; parental origin; GTF2I INTRODUCTION As an approach toward understanding the role of the deleted genes William’s syndrome (WS) is a neurogenetic disorder affecting human in WS, we have characterized WS subjects according to genetic, social/ development and adult cognition. -
Claudin-2: Roles Beyond Permeability Functions
International Journal of Molecular Sciences Review Claudin-2: Roles beyond Permeability Functions Shruthi Venugopal, Shaista Anwer and Katalin Szászi * Keenan Research Centre for Biomedical Science of the St. Michael’s Hospital and Department of Surgery, University of Toronto, Toronto, ON M5B 1W8, Canada; [email protected] (S.V.); [email protected] (S.A.) * Correspondence: [email protected]; Tel.: +1-416-8471752 Received: 13 October 2019; Accepted: 9 November 2019; Published: 12 November 2019 Abstract: Claudin-2 is expressed in the tight junctions of leaky epithelia, where it forms cation-selective and water permeable paracellular channels. Its abundance is under fine control by a complex signaling network that affects both its synthesis and turnover in response to various environmental inputs. Claudin-2 expression is dysregulated in many pathologies including cancer, inflammation, and fibrosis. Claudin-2 has a key role in energy-efficient ion and water transport in the proximal tubules of the kidneys and in the gut. Importantly, strong evidence now also supports a role for this protein as a modulator of vital cellular events relevant to diseases. Signaling pathways that are overactivated in diseases can alter claudin-2 expression, and a good correlation exists between disease stage and claudin-2 abundance. Further, loss- and gain-of-function studies showed that primary changes in claudin-2 expression impact vital cellular processes such as proliferation, migration, and cell fate determination. These effects appear to be mediated by alterations in key signaling pathways. The specific mechanisms linking claudin-2 to these changes remain poorly understood, but adapters binding to the intracellular portion of claudin-2 may play a key role. -
Computational Modeling of Claudin Structure and Function
International Journal of Molecular Sciences Review Computational Modeling of Claudin Structure and Function Shadi Fuladi 1, Ridaka-Wal Jannat 1 , Le Shen 2,3 , Christopher R. Weber 2,* and Fatemeh Khalili-Araghi 1,* 1 Department of Physics, University of Illinois at Chicago, Chicago, IL 60607, USA; [email protected] (S.F.); [email protected] (R.-W.J.) 2 Department of Pathology, University of Chicago, Chicago, IL 60637, USA; [email protected] 3 Department of Surgery, University of Chicago, Chicago, IL 60637, USA * Correspondence: [email protected] (C.R.W.); [email protected] (F.K.-A.) Received: 15 December 2019; Accepted: 16 January 2020; Published: 23 January 2020 Abstract: Tight junctions form a barrier to control passive transport of ions and small molecules across epithelia and endothelia. In addition to forming a barrier, some of claudins control transport properties of tight junctions by forming charge- and size-selective ion channels. It has been suggested claudin monomers can form or incorporate into tight junction strands to form channels. Resolving the crystallographic structure of several claudins in recent years has provided an opportunity to examine structural basis of claudins in tight junctions. Computational and theoretical modeling relying on atomic description of the pore have contributed significantly to our understanding of claudin pores and paracellular transport. In this paper, we review recent computational and mathematical modeling of claudin barrier function. We focus on dynamic modeling of global epithelial barrier function as a function of claudin pores and molecular dynamics studies of claudins leading to a functional model of claudin channels. Keywords: claudin; molecular dynamics; tight junction; ion transport; ion channel 1. -
Salinity Regulates Claudin Mrna and Protein Expression in the Teleost Gill
View metadata, citation and similar papers at core.ac.uk brought to you by CORE Am J Physiol Regul Integr Comp Physiol 294: R1004–R1014, 2008. provided by University of Southern Denmark Research Output First published January 9, 2008; doi:10.1152/ajpregu.00112.2007. Salinity regulates claudin mRNA and protein expression in the teleost gill Christian K. Tipsmark,* David A. Baltzegar,* Ozkan Ozden, Brenda J. Grubb, and Russell J. Borski Department of Zoology, North Carolina State University, Raleigh, North Carolina Submitted 14 February 2007; accepted in final form 19 December 2007 Tipsmark CK, Baltzegar DA, Ozden O, Grubb BJ, Borski RJ. The biochemical basis for changes in water permeability may Salinity regulates claudin mRNA and protein expression in the teleost entail the robust downregulation of gill aquaporin mRNA and gill. Am J Physiol Regul Integr Comp Physiol 294: R1004–R1014, 2008. protein expression that accompanies SW acclimation in eel (6, First published January 9, 2008; doi:10.1152/ajpregu.00112.2007.—The 21). Although osmotic permeability decreases in SW, the teleost gill carries out NaCl uptake in freshwater (FW) and NaCl conductance and short-circuit current is found to be larger in a excretion in seawater (SW). This transformation with salinity requires close regulation of ion transporter capacity and epithelial permeabil- SW teleost compared with a FW fish (8, 27). A simultaneous change in the ultrastructure of tight junctions (TJs) is also seen Downloaded from ity. This study investigates the regulation of tight-junctional claudins ϩ during salinity acclimation in fish. We identified claudin 3- and (28). Secretion of Na is thought to involve a paracellular claudin 4-like immunoreactive proteins and examined their expression path confined to thin “leaky” TJs that occur in SW between and that of select ion transporters by performing Western blot in mature chloride cells and accessory cells (19, 36), and this tilapia (Oreochromis mossambicus) gill during FW and SW acclima- may contribute to the relatively high ionic permeability of tion. -
Analysis of the Indacaterol-Regulated Transcriptome in Human Airway
Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/04/13/jpet.118.249292.DC1 1521-0103/366/1/220–236$35.00 https://doi.org/10.1124/jpet.118.249292 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:220–236, July 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Analysis of the Indacaterol-Regulated Transcriptome in Human Airway Epithelial Cells Implicates Gene Expression Changes in the s Adverse and Therapeutic Effects of b2-Adrenoceptor Agonists Dong Yan, Omar Hamed, Taruna Joshi,1 Mahmoud M. Mostafa, Kyla C. Jamieson, Radhika Joshi, Robert Newton, and Mark A. Giembycz Departments of Physiology and Pharmacology (D.Y., O.H., T.J., K.C.J., R.J., M.A.G.) and Cell Biology and Anatomy (M.M.M., R.N.), Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Received March 22, 2018; accepted April 11, 2018 Downloaded from ABSTRACT The contribution of gene expression changes to the adverse and activity, and positive regulation of neutrophil chemotaxis. The therapeutic effects of b2-adrenoceptor agonists in asthma was general enriched GO term extracellular space was also associ- investigated using human airway epithelial cells as a therapeu- ated with indacaterol-induced genes, and many of those, in- tically relevant target. Operational model-fitting established that cluding CRISPLD2, DMBT1, GAS1, and SOCS3, have putative jpet.aspetjournals.org the long-acting b2-adrenoceptor agonists (LABA) indacaterol, anti-inflammatory, antibacterial, and/or antiviral activity. Numer- salmeterol, formoterol, and picumeterol were full agonists on ous indacaterol-regulated genes were also induced or repressed BEAS-2B cells transfected with a cAMP-response element in BEAS-2B cells and human primary bronchial epithelial cells by reporter but differed in efficacy (indacaterol $ formoterol . -
Defenders and Challengers of Endothelial Barrier Function
REVIEW published: 18 December 2017 doi: 10.3389/fimmu.2017.01847 Defenders and Challengers of Endothelial Barrier Function Nader Rahimi* Department of Pathology, Boston University School of Medicine, Boston, MA, United States Regulated vascular permeability is an essential feature of normal physiology and its dysfunction is associated with major human diseases ranging from cancer to inflam- mation and ischemic heart diseases. Integrity of endothelial cells also play a prominent role in the outcome of surgical procedures and organ transplant. Endothelial barrier function and integrity are regulated by a plethora of highly specialized transmembrane receptors, including claudin family proteins, occludin, junctional adhesion molecules (JAMs), vascular endothelial (VE)-cadherin, and the newly identified immunoglobulin (Ig) and proline-rich receptor-1 (IGPR-1) through various distinct mechanisms and signaling. On the other hand, vascular endothelial growth factor (VEGF) and its tyrosine kinase receptor, VEGF receptor-2, play a central role in the destabilization of endothelial barrier function. While claudins and occludin regulate cell–cell junction via recruitment of zonula occludens (ZO), cadherins via catenin proteins, and JAMs via ZO and afadin, IGPR-1 recruits bullous pemphigoid antigen 1 [also called dystonin (DST) and SH3 protein inter- Edited by: acting with Nck90/WISH (SH3 protein interacting with Nck)]. Endothelial barrier function Thomas Luft, is moderated by the function of transmembrane receptors and signaling events that act University Hospital Heidelberg, Germany to defend or destabilize it. Here, I highlight recent advances that have provided new Reviewed by: insights into endothelial barrier function and mechanisms involved. Further investigation Luiza Guilherme, of these mechanisms could lead to the discovery of novel therapeutic targets for human University of São Paulo, Brazil diseases associated with endothelial dysfunction. -
Adherens Junctions, Desmosomes and Tight Junctions in Epidermal Barrier Function Johanna M
14 The Open Dermatology Journal, 2010, 4, 14-20 Open Access Adherens Junctions, Desmosomes and Tight Junctions in Epidermal Barrier Function Johanna M. Brandner1,§, Marek Haftek*,2,§ and Carien M. Niessen3,§ 1Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany 2University of Lyon, EA4169 Normal and Pathological Functions of Skin Barrier, E. Herriot Hospital, Lyon, France 3Department of Dermatology, Center for Molecular Medicine, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany Abstract: The skin is an indispensable barrier which protects the body from the uncontrolled loss of water and solutes as well as from chemical and physical assaults and the invasion of pathogens. In recent years several studies have suggested an important role of intercellular junctions for the barrier function of the epidermis. In this review we summarize our knowledge of the impact of adherens junctions, (corneo)-desmosomes and tight junctions on barrier function of the skin. Keywords: Cadherins, catenins, claudins, cell polarity, stratum corneum, skin diseases. INTRODUCTION ADHERENS JUNCTIONS The stratifying epidermis of the skin physically separates Adherens junctions are intercellular structures that couple the organism from its environment and serves as its first line intercellular adhesion to the cytoskeleton thereby creating a of structural and functional defense against dehydration, transcellular network that coordinate the behavior of a chemical substances, physical insults and micro-organisms. population of cells. Adherens junctions are dynamic entities The living cell layers of the epidermis are crucial in the and also function as signal platforms that regulate formation and maintenance of the barrier on two different cytoskeletal dynamics and cell polarity. -
Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in -
Tight Junction-Based Epithelial Microenvironment and Cell Proliferation
Oncogene (2008) 27, 6930–6938 & 2008 Macmillan Publishers Limited All rights reserved 0950-9232/08 $32.00 www.nature.com/onc REVIEW Tight junction-based epithelial microenvironment and cell proliferation S Tsukita1, Y Yamazaki, T Katsuno, A Tamura and S Tsukita2 Laboratory of Biological Science, Graduate School of Frontier Biosciences/Graduate School of Medicine, Osaka University, Suita, Osaka, Japan Belt-like tight junctions (TJs), referred to as zonula bodies of multicellular organisms. The sheet-like divi- occludens, have long been regarded as a specialized sions allow diffusion barrier formation and selective differentiation of epithelial cell membranes. They are permeation of substances and ions (permselectivity), required for cell adhesion and paracellular barrier func- both excluding unnecessary or toxic molecules and tions, and are now thought to be partly involved in fence including necessary components to maintain home- functions and in cell polarization. Recently, the molecular ostasis. The combination of the belt-like adherens bases of TJs have gradually been unveiled. TJs are junctions (AJs) and tight junctions (TJs) have important constructed by TJ strands, whose basic frameworks are functions in the formation of epithelial cell sheets and composed of integral membrane proteins with four also in the formation of paracellular permselective transmembrane domains, designated claudins. The claudin barriers through their functions as septa (Mitic and family is supposedly composed of at least 24 members in Anderson, 1998; Tsukita and Furuse, 1999; Hartsock mice and humans. Other types of integral membrane and Nelson, 2008). Paracellular barrier functions with proteins with four transmembrane domains, namely occlu- permselectivity are unique to the epithelial cell system din and tricellulin, as well as the single transmembrane and regulate the internal homeostasis of ions and solutes proteins, JAMs (junctional adhesion molecules)and CAR in the body. -
Claudin-1, -3 and -4 Proteins and Mrna Expression in Benign and Malignant Breast Lesions: a Research Study
Available online http://breast-cancer-research.com/content/7/2/R296 ResearchVol 7 No 2 article Open Access Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study Anna-Mária Tőkés1*, Janina Kulka1*, Sándor Paku2, Ágnes Szik1, Csilla Páska1, Pál Kaposi Novák1, László Szilák1, András Kiss1, Krisztina Bögi1 and Zsuzsa Schaff1 12nd Department of Pathology, Semmelweis University, Budapest, Hungary 2Department of Molecular Pathology, Joint Research Organization of the Hungarian Academy of Sciences, Budapest, Hungary * Contributed equally Corresponding author: Janina Kulka, [email protected] Received: 23 Jan 2004 Revisions requested: 15 Mar 2004 Revisions received: 1 Oct 2004 Accepted: 2 Dec 2004 Published: 31 Jan 2005 Breast Cancer Research 2005, 7:R296-R305 (DOI 10.1186/bcr983)http://breast-cancer-research.com/content/7/2/R296 © 2005 Tőkés et al., licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is cited. Abstract Introduction We compared levels of protein and mRNA CLDN4 was present in all 56 tissue sections. However, CLDN4 expression of three members of the claudin (CLDN) family in was highly positive in normal epithelial cells and was decreased malignant breast tumours and benign lesions. or absent in 17 out of 21 ductal carcinoma grade 1, in special types of breast carcinoma (mucinous, papillary, tubular) and in Methods Altogether, 56 sections from 52 surgically resected areas of apocrine metaplasia. -
Identification of Claudin 1 Transcript Variants in Human Invasive Breast Cancer
RESEARCH ARTICLE Identification of Claudin 1 Transcript Variants in Human Invasive Breast Cancer Anne A. Blanchard1,2, Teresa Zelinski3,4, Jiuyong Xie2, Steven Cooper1, Carla Penner1, Etienne Leygue4,5, Yvonne Myal1,2,5* 1 Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada, 2 Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada, 3 Departmentof Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada, 4 Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada, 5 Manitoba Institute of Cell Biology, Winnipeg, Manitoba, Canada * [email protected] a11111 Abstract Background The claudin 1 tight junction protein, solely responsible for the barrier function of epithelial cells, is frequently down regulated in invasive human breast cancer. The underlying mecha- OPEN ACCESS nism is largely unknown, and no obvious mutations in the claudin 1 gene (CLDN1) have Citation: Blanchard AA, Zelinski T, Xie J, Cooper S, been identified to date in breast cancer. Since many genes have been shown to undergo Penner C, Leygue E, et al. (2016) Identification of deregulation through splicing and mis-splicing events in cancer, the current study was Claudin 1 Transcript Variants in Human Invasive undertaken to investigate the occurrence of transcript variants for CLDN1 in human invasive Breast Cancer. PLoS ONE 11(9): e0163387. breast cancer. doi:10.1371/journal.pone.0163387 Editor: Amanda Ewart Toland, Ohio State University Wexner Medical Center, UNITED STATES Methods Received: May 17, 2016 RT-PCR analysis of CLDN1 transcripts was conducted on RNA isolated from 12 human invasive breast tumors. The PCR products from each tumor were resolved by agarose gel Accepted: September 6, 2016 electrophoresis, cloned and sequenced.