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<a href="http://doi.org/10.1096/fasebj.2020.34.s1.05298" target="_blank" rel="noreferrer noopener">http://doi.org/10.1096/fasebj.2020.34.s1.05298</a>
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1
Volume
34
ISSN
0892-6638
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<a href="http://neomed.idm.oclc.org/login?url=http://doi.org/10.1096/fasebj.2020.34.s1.05298" target="_blank" rel="noreferrer noopener">NEOMED Full-text Holding (if available) - Proxy DOI: 10.1096/fasebj.2020.34.s1.05298</a>
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Update Year & Number
September 2020 List
NEOMED College
NEOMED College of Medicine
NEOMED Department
NEOMED Student Publications
Department of Integrative Medical Sciences
Dublin Core
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Title
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Smooth muscle‐specific deletion of O‐GlcNAc transferase inhibits SMC de‐differentiation in STZ‐induced hyperglycemic mice
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Faseb Journal
Date
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2020
2020-04
Creator
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Khanal S;Mathias A;Lallo Jason;Ferrell J;Ohanyan V;Raman P
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Vascular smooth muscle cell (VSMC) migration and proliferation, hallmark of SMC phenotypic switching central to the evolution of atherosclerosis, is profoundly enhanced in diabetic patients. Hyperglycemia, characteristic of diabetes, increases glucose flux through the hexosamine metabolic pathway triggering an enhanced signaling via O‐linked N‐acetylglucosamine (O‐GlcNAc) transferase (OGT), key regulator of protein O‐GlcNAcylation. Multiple studies, including ours, support an association between O‐GlcNAcylation and diabetes‐related complications. However, the role of OGT in VSMC activation in diabetes remains elusive. The goal of the present study was to interrogate whether OGT plays a direct role in SMC de‐differentiation in hyperglycemic mice in vivo. Briefly, we crossed OGTfl/fl female mice with tamoxifen‐inducible Myh11‐Cre ERT2 male mice (Cretg); the resulting Cretg/OGTfl/Y males (produced in F1 generation) were used for Cre recombinase activation. Specifically, Cretg/OGTfl/Y and age‐matched Cretg/OGT+/Y littermates at 6 wks age were injected i.p. with tamoxifen (60mg/kg/day) or peanut oil (vehicle control) once daily for 5 consecutive days. Two weeks post‐tamoxifen, mice genotypes received low‐dose STZ (50mg/Kg/day, i.p) or vehicle (citrated buffer) once daily for 5 consecutive days for induction of hyperglycemia. At 16 wks age, mice were subjected to metabolic profiling and cardiac function studies followed by plasma, heart and aortic tissue harvests. Immunoblotting of aortic lysates confirmed loss of OGT expression in tamoxifen‐treated Cretg/OGTfl/Y (smOGT−/Y) mice compared to vehicle‐treated Cretg/OGTfl/Y littermates and tamoxifen‐treated OGTfl/Y mice (smOGT+/Y, with intact OGT). In contrast, OGT expression was unaltered in left ventricular tissue lysates derived from smOGT−/Y vs. smOGT+/Y mice, validating our SMC‐specific OGT knockout mouse model. Immunoblotting further revealed augmented α‐SMA and Calponin expression (SM contractile markers) in aortic vessels of hyperglycemic smOGT−/Y vs. hyperglycemic smOGT+/Y mice. This was accompanied with attenuated PCNA (proliferation marker) and Vimentin (SM synthetic marker) expression in aortic vasculature of smOGT−/Y vs smOGT+/Y mice, under conditions of hyperglycemia. Importantly, increased α‐SMA and Calponin expression occured concomitant to reduced YY1 (transcriptional repressor of SM contractile genes) expression in aortic vessels of smOGT−/Y vs. smOGT+/Y mice, in response to STZ‐induced hyperglycemia. Interestingly, SMC‐specific OGT deletion had no effect on cardiac function of the mice genotypes under basal and hyperglycemic conditions, shown via Echocardiography. Moreover, hyperglycemic smOGT−/Y mice revealed a time‐dependent increase in energy expenditure reflected in differences in O2 consumption and CO2 production compared to hyperglycemic smOGT+/Y mice, depicted via CLAMS studies. Taken together, our results demonstrate a direct regulatory role of OGT on VSMC phenotypic transformation in response to hyperglycemia. Overall, the current study suggests OGT as a potential target in diabetic atherosclerotic disease.
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<a href="http://doi.org/10.1096/fasebj.2020.34.s1.05298" target="_blank" rel="noreferrer noopener">10.1096/fasebj.2020.34.s1.05298</a>
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journalArticle
2020
Department of Integrative Medical Sciences
Faseb Journal
Ferrell J
journalArticle
Khanal S
Lallo Jason
Mathias A
NEOMED College of Medicine
NEOMED College of Medicine Student
NEOMED Student Publications
Ohanyan V
Raman P
September 2020 List
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
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n/a
Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Pages
2-2
Volume
30
Search for Full-text
Locate full-text within NEOMED Library's e-journal collections
<p>Users with a NEOMED Library login can search for full-text journal articles at the following url: <a href="https://libraryguides.neomed.edu/home">https://libraryguides.neomed.edu/home</a></p>
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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Cholesterol 7 Alpha-hydroxylase (cyp7a1) Plays A Critical Role In Preventing Hepatic Inflammation And Fibrosis
Publisher
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Faseb Journal
Date
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2016
2016-04
Subject
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Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Creator
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Liu H L; Ferrell J; Boehme S; Chiang J
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n/a
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Journal Article or Conference Abstract Publication
2016
Biochemistry & Molecular Biology
Boehme S
Cell Biology
Chiang J
Faseb Journal
Ferrell J
Journal Article or Conference Abstract Publication
Life Sciences & Biomedicine - Other
Liu H L
Topics