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ADAM17 mediates Nox4 expression and NADPH oxidase activity in the kidney cortex of OVE26 mice

Show simple item record Ford B.M. Eid A.A. Gooz M. Barnes J.L. Gorin Y.C. Abboud H.E.
dc.contributor.editor 2013 2017-09-07T07:00:00Z 2017-09-07T07:00:00Z 2013
dc.identifier 10.1152/ajprenal.00522.2012
dc.identifier.issn 03636127
dc.description.abstract Matrix protein accumulation is a prominent feature of diabetic nephropathy that contributes to renal fibrosis and decline in renal function. The pathogenic mechanisms of matrix accumulation are incompletely characterized. We investigated if the matrix metalloprotease a disintegrin and metalloprotease1 7 (ADAM17), known to cleave growth factors and cytokines, is activated in the kidney cortex of OVE26 type 1 diabetic mice and the potential mechanisms by which ADAM17 mediates extracellular matrix accumulation. Protein expression and activity of ADAM17 were increased in OVE26 kidney cortex. Using a pharmacological inhibitor to ADAM17, TMI-005, we determined that ADAM17 activation results in increased type IV collagen, Nox4, and NADPH oxidase activity in the kidney cortex of diabetic mice. In cultured mouse proximal tubular epithelial cells (MCTs), high glucose increases ADAM17 activity, Nox4 and fibronectin expression, cellular collagen content, and NADPH oxidase activity. These effects of glucose were inhibited when cells were pretreated with TMI-005 and-or transfected with small interfering ADAM17. Collectively, these data indicate a novel mechanism whereby hyperglycemia in diabetes increases extracellular matrix protein expression in the kidney cortex through activation of ADAM17 and enhanced oxidative stress through Nox enzyme activation. Additionally, our study is the first to provide evidence that Nox4 is downstream of ADAM17.
dc.language English
dc.publisher BETHESDA
dc.relation.ispartof Publication Name: American Journal of Physiology - Renal Physiology; Publication Year: 2013; Volume: 305; no. 3;
dc.source Scopus
dc.title ADAM17 mediates Nox4 expression and NADPH oxidase activity in the kidney cortex of OVE26 mice
dc.type Article
dc.contributor.affiliation Ford, B.M., Department of Medicine, Division of Nephrology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
dc.contributor.affiliation Eid, A.A., Department of Medicine, Division of Nephrology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Göoz, M., Department of Medicine, Medical University of South Carolina, Charleston, CA, United States
dc.contributor.affiliation Barnes, J.L., Department of Medicine, Division of Nephrology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, South Texas Veterans Healthcare System, San Antonio, TX, United States
dc.contributor.affiliation Gorin, Y.C., Department of Medicine, Division of Nephrology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
dc.contributor.affiliation Abboud, H.E., Department of Medicine, Division of Nephrology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, South Texas Veterans Healthcare System, San Antonio, TX, United States
dc.contributor.authorAddress Abboud, H. E.; Dept. of Medicine, Division of Nephrology, UT Health Science Center at San Antonio, San Antonio, TX, United States; email:
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Anatomy, Cell Biology and Physiological Sciences;
dc.contributor.authorDepartment Anatomy, Cell Biology and Physiological Sciences
dc.contributor.faculty Faculty of Medicine
dc.contributor.authorInitials Ford, BM
dc.contributor.authorInitials Eid, AA
dc.contributor.authorInitials Gooz, M
dc.contributor.authorInitials Barnes, JL
dc.contributor.authorInitials Gorin, YC
dc.contributor.authorInitials Abboud, HE
dc.contributor.authorReprintAddress Abboud, HE (reprint author), UT Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX USA.
dc.contributor.authorUniversity American University of Beirut Medical Center
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dc.description.citedCount 6
dc.description.citedTotWOSCount 7
dc.description.citedWOSCount 7
dc.identifier.coden AJPPF
dc.identifier.pubmedID 23678045
dc.identifier.scopusID 84881008965
dc.publisher.address 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
dc.relation.ispartOfISOAbbr Am. J. Physiol.-Renal Physiol.
dc.relation.ispartOfIssue 3
dc.relation.ispartofPubTitle American Journal of Physiology - Renal Physiology
dc.relation.ispartofPubTitleAbbr Am. J. Physiol. Renal Physiol.
dc.relation.ispartOfVolume 305
dc.source.ID WOS:000322699000012
dc.type.publication Journal
dc.subject.otherAuthKeyword ADAM17
dc.subject.otherAuthKeyword Diabetic nephropathy
dc.subject.otherAuthKeyword Extracellular matrix
dc.subject.otherAuthKeyword Nox4
dc.subject.otherAuthKeyword OVE26 mice
dc.subject.otherChemCAS apratastat, 287405-51-0
dc.subject.otherChemCAS collagen, 9007-34-5
dc.subject.otherChemCAS fibronectin, 86088-83-7
dc.subject.otherChemCAS glucose, 50-99-7, 84778-64-3
dc.subject.otherChemCAS reduced nicotinamide adenine dinucleotide phosphate oxidase, 9032-22-8
dc.subject.otherChemCAS ADAM Proteins, 3.4.24.-
dc.subject.otherChemCAS Collagen, 9007-34-5
dc.subject.otherChemCAS Collagen Type IV
dc.subject.otherChemCAS Fibronectins
dc.subject.otherChemCAS Glucose, IY9XDZ35W2
dc.subject.otherChemCAS NADPH Oxidase,
dc.subject.otherChemCAS Nox4 protein, mouse, 1.6.-
dc.subject.otherChemCAS RNA, Small Interfering
dc.subject.otherChemCAS tumor necrosis factor-alpha convertase, 3.4.24.-
dc.subject.otherIndex ADAM protein
dc.subject.otherIndex ADAM17 protein
dc.subject.otherIndex apratastat
dc.subject.otherIndex collagen
dc.subject.otherIndex collagen type 4
dc.subject.otherIndex cytokine
dc.subject.otherIndex fibronectin
dc.subject.otherIndex glucose
dc.subject.otherIndex growth factor
dc.subject.otherIndex reduced nicotinamide adenine dinucleotide phosphate oxidase
dc.subject.otherIndex reduced nicotinamide adenine dinucleotide phosphate oxidase 4
dc.subject.otherIndex unclassified drug
dc.subject.otherIndex animal experiment
dc.subject.otherIndex animal model
dc.subject.otherIndex animal tissue
dc.subject.otherIndex article
dc.subject.otherIndex controlled study
dc.subject.otherIndex enzyme activation
dc.subject.otherIndex epithelium cell
dc.subject.otherIndex extracellular matrix
dc.subject.otherIndex hyperglycemia
dc.subject.otherIndex insulin dependent diabetes mellitus
dc.subject.otherIndex kidney cortex
dc.subject.otherIndex male
dc.subject.otherIndex mouse
dc.subject.otherIndex nonhuman
dc.subject.otherIndex priority journal
dc.subject.otherIndex protein expression
dc.subject.otherIndex ADAM17
dc.subject.otherIndex diabetic nephropathy
dc.subject.otherIndex extracellular matrix
dc.subject.otherIndex Nox4
dc.subject.otherIndex OVE26 mice
dc.subject.otherIndex ADAM Proteins
dc.subject.otherIndex Animals
dc.subject.otherIndex Blotting, Western
dc.subject.otherIndex Body Weight
dc.subject.otherIndex Collagen
dc.subject.otherIndex Collagen Type IV
dc.subject.otherIndex Diabetes Mellitus, Type 1
dc.subject.otherIndex Fibronectins
dc.subject.otherIndex Fluorescent Antibody Technique
dc.subject.otherIndex Glucose
dc.subject.otherIndex Immunoenzyme Techniques
dc.subject.otherIndex Kidney Cortex
dc.subject.otherIndex Male
dc.subject.otherIndex Mice
dc.subject.otherIndex NADPH Oxidase
dc.subject.otherIndex Organ Size
dc.subject.otherIndex RNA, Small Interfering
dc.subject.otherKeywordPlus EPIDERMAL-GROWTH-FACTOR
dc.subject.otherKeywordPlus NECROSIS-FACTOR-ALPHA
dc.subject.otherKeywordPlus SMOOTH-MUSCLE-CELLS
dc.subject.otherKeywordPlus CONVERTING-ENZYME
dc.subject.otherKeywordPlus FACTOR RECEPTOR
dc.subject.otherKeywordPlus NAD(P)H OXIDASE
dc.subject.otherKeywordPlus MESANGIAL CELLS
dc.subject.otherKeywordPlus ANGIOTENSIN-II
dc.subject.otherKeywordPlus UP-REGULATION
dc.subject.otherKeywordPlus HIGH GLUCOSE
dc.subject.otherWOS Physiology
dc.subject.otherWOS Urology and Nephrology

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