| Renal tubular angiogenic dysregulation in anti-Thy1.1 glomerulonephritis. | |
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MedLine Citation:
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PMID: 21048020 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Peritubular vascular changes and hypoxia after glomerular injury may explain subsequent tubulointerstitial injury and fibrosis. Several studies suggested that the expected tubulointerstitial angiogenic response is actively suppressed in this setting. The mechanism of this aberrant response has not been clearly identified. We used a common model of glomerular injury in rats to assess vascular changes and to identify potential factors associated with this aberrant response. Anti-Thy1.1 antibody administration (1 or 4 weekly doses) led to a dose-dependent renal damage characterized by elevated urea and tubulointerstitial fibrosis as assessed by Picro-Sirius Red staining. We quantified peritubular capillaries using CD31 and CD34 immunohistochemistry and showed that tubular angiogenic dysregulation was associated with peritubular capillary rarefaction. Using laser capture microdissection, we demonstrated an early induction of fibrogenic and angiogenic factors in the glomeruli and a subsequent dysregulated angiogenic response in the tubulointerstitial compartment. Proximal tubules of anti-Thy1.1-treated animals had increased pigment epithelial-derived factor (PEDF) expression by immunohistochemistry. Protein taken by laser capture microdissection also showed that PEDF was upregulated. Temporally associated with PEDF expression was a transient downregulation of tubular hypoxia-inducible factor (HIF)1α. In a human proximal tubular cell culture, we show that PEDF downregulates HIF1α protein and gene expression in cells exposed to 1% oxygen. In anti-Thy1.1 glomerulonephritis, there is aberrent tubular angiogenesis associated with glomerular injury and tubulointersititial fibrosis. We showed that PEDF may be involved by downregulating HIF1α. Further work is needed to elucidate the mechanism of PEDF upregulation and action in the tubules. |
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Authors:
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Davide P Cina; Hui Xu; Limin Liu; Laszlo Farkas; Daniela Farkas; Martin Kolb; Peter J Margetts |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-03 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: 300 ISSN: 1522-1466 ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-04 Completed Date: 2011-03-30 Revised Date: 2011-04-28 |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: United States |
Other Details:
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Languages: eng Pagination: F488-98 Citation Subset: IM |
Affiliation:
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Department of Medicine, McMaster University, Hamilton, Ontario, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD31 / analysis, immunology Antigens, CD34 / analysis, immunology Antigens, Thy-1 / immunology Cell Line Down-Regulation Eye Proteins / metabolism Female Glomerulonephritis / pathology, physiopathology* Humans Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Kidney Failure, Chronic / physiopathology Kidney Tubules, Proximal / blood supply, pathology, physiopathology* Neovascularization, Pathologic / physiopathology* Nerve Growth Factors / metabolism Rats Rats, Sprague-Dawley Serpins / metabolism Up-Regulation Urea / blood Vascular Endothelial Growth Factor A / analysis, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD31; 0/Antigens, CD34; 0/Antigens, Thy-1; 0/Eye Proteins; 0/Hif1a protein, rat; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Nerve Growth Factors; 0/Serpins; 0/Vascular Endothelial Growth Factor A; 0/pigment epithelium-derived factor; 57-13-6/Urea |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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