| Glomerular protein levels of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 are lower in diabetic subjects. | |
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MedLine Citation:
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PMID: 19506087 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate extracellular matrix turnover throughout the body, including in renal glomeruli. We investigated protein levels of multiple MMPs (MMP-1, MMP-2, MMP-3, and MMP-9) and TIMP-1 in glomeruli and investigated whether disease phenotypes were associated with levels of these proteins. Renal cortex was collected from 100 adult autopsy subjects arrayed across 17 tissue microarrays. Immunohistochemical staining intensity for each MMP and TIMP-1 was determined using quantitative color deconvolution techniques. We observed significantly decreased glomerular MMP-1 and TIMP-1 staining in subjects with diabetes, hypertension, and an estimated glomerular filtration rate <30 ml/min/1.73 m(2) in univariate analyses. MMP-1 staining, but not TIMP-1 staining, was inversely correlated with increased glomerular fibrosis (r = -0.40). In multivariable analysis, diabetes was robustly associated with decreased staining intensity. This study indicates that in human subjects, the long-term sequelae of diseases such as diabetes that cause chronic renal failure result in decreased TIMP-1 and MMP-1 proteins in renal glomeruli. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. |
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Authors:
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Toby C Cornish; Serena M Bagnasco; Anne M Macgregor; Jie Lu; Elizabeth Selvin; Marc K Halushka |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-06-08 |
Journal Detail:
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Title: The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society Volume: 57 ISSN: 1551-5044 ISO Abbreviation: J. Histochem. Cytochem. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-19 Completed Date: 2009-11-17 Revised Date: 2011-09-07 |
Medline Journal Info:
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Nlm Unique ID: 9815334 Medline TA: J Histochem Cytochem Country: United States |
Other Details:
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Languages: eng Pagination: 995-1001 Citation Subset: IM |
Affiliation:
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Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Analysis of Variance Antibodies / immunology Color Diabetes Mellitus / metabolism*, pathology, physiopathology Female Fibrosis / complications Humans Immunohistochemistry Kidney Diseases / complications Kidney Glomerulus / metabolism*, pathology Male Matrix Metalloproteinase 1 / immunology, metabolism* Middle Aged Staining and Labeling Tissue Array Analysis Tissue Inhibitor of Metalloproteinase-1 / immunology, metabolism* Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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K-01 DK-076595/DK/NIDDK NIH HHS; K01 DK076595-01/DK/NIDDK NIH HHS; K01 DK076595-02/DK/NIDDK NIH HHS; K01 DK076595-03/DK/NIDDK NIH HHS; K01 DK076595-04/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/Tissue Inhibitor of Metalloproteinase-1; EC 3.4.24.7/Matrix Metalloproteinase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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