| High glucose upregulates upstream stimulatory factor 2 in human renal proximal tubular cells through angiotensin II-dependent activation of CREB. | |
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MedLine Citation:
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PMID: 20814220 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: We have previously demonstrated that a transcription factor, upstream stimulatory factor 2 (USF2), regulates glucose-induced thrombospondin 1 expression and transforming growth factor-β activity in mesangial cells, and plays an important role in diabetic glomerulopathy. In this study, we determined whether USF2 expression in renal proximal tubular cells is regulated by glucose and contributes to diabetic tubulointerstitial fibrosis. METHODS: Human renal proximal tubular cells (HK-2 cells) were treated with normal- or high-glucose medium for 24 h. After treatment, real-time PCR or immunoblotting was used to determine the expression of USF2 and other components of the renin-angiotensin system in HK-2 cells. RESULTS: High glucose upregulated USF2 expression and increased extracellular matrix accumulation in HK-2 cells; both were inhibited by siRNA-mediated USF2 knockdown. In addition, high glucose stimulated angiotensinogen and renin expression, increased renin activity, and resulted in increased angiotensin II formation. Treatment of HK-2 cells with an angiotensin II receptor 1 (AT1) blocker--losartan--prevented high-glucose-induced USF2 expression and high-glucose-enhanced phosphorylation of CREB (cAMP response element-binding protein). CONCLUSION: Our data established that high glucose stimulated USF2 expression in HK-2 cells, at least in part, through angiotensin II-AT1-dependent activation of CREB, which can contribute to diabetic tubulointerstitial fibrosis. |
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Authors:
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Nishant P Visavadiya; Yanzhang Li; Shuxia Wang |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-01 |
Journal Detail:
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Title: Nephron. Experimental nephrology Volume: 117 ISSN: 1660-2129 ISO Abbreviation: Nephron Exp. Nephrol. Publication Date: 2011 |
Date Detail:
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Created Date: 2011-03-01 Completed Date: 2011-06-17 Revised Date: 2012-01-02 |
Medline Journal Info:
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Nlm Unique ID: 101159770 Medline TA: Nephron Exp Nephrol Country: Switzerland |
Other Details:
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Languages: eng Pagination: e62-70 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 S. Karger AG, Basel. |
Affiliation:
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Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40536-0200, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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metabolism Cell Line Cyclic AMP Response Element-Binding Protein / metabolism* Diabetic Nephropathies / physiopathology Glucose / administration & dosage*, pharmacology Humans Kidney Tubules, Proximal / cytology, metabolism*, physiopathology Losartan / pharmacology Peptidyl-Dipeptidase A / metabolism Renin / biosynthesis Renin-Angiotensin System Up-Regulation Upstream Stimulatory Factors / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK081555/DK/NIDDK NIH HHS; R01 DK081555-02/DK/NIDDK NIH HHS; R01 DK081555-03/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclic AMP Response Element-Binding Protein; 0/USF2 protein, human; 0/Upstream Stimulatory Factors; 11128-99-7/Angiotensin II; 114798-26-4/Losartan; 50-99-7/Glucose; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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