Glomerular protein levels of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 are lower in diabetic subjects. J Histochem Cytochem 2009 Nov;57(11):995-1001
Date
06/10/2009Pubmed ID
19506087Pubmed Central ID
PMC2762888DOI
10.1369/jhc.2009.954107Scopus ID
2-s2.0-70449727044 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
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.
Author List
Cornish TC, Bagnasco SM, Macgregor AM, Lu J, Selvin E, Halushka MKAuthor
Toby Charles Cornish MD, PhD Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Analysis of Variance
Antibodies
Color
Diabetes Mellitus
Female
Fibrosis
Humans
Immunohistochemistry
Kidney Diseases
Kidney Glomerulus
Male
Matrix Metalloproteinase 1
Middle Aged
Staining and Labeling
Tissue Array Analysis
Tissue Inhibitor of Metalloproteinase-1
Young Adult
