Journal of Histochemistry and Cytochemistry
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Originally published as JHC exPRESS on June 8, 2009.
doi:10.1369/jhc.2009.954107
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Journal of Histochemistry and Cytochemistry
Volume 57 (11): 995-1001, 2009
Copyright ©The Histochemical Society, Inc.

Glomerular Protein Levels of Matrix Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinase-1 Are Lower in Diabetic Subjects

Toby C. Cornish, Serena M. Bagnasco, Anne M. Macgregor, Jie Lu, Elizabeth Selvin and Marc K. Halushka

Department of Pathology (TCC,SMB,AMM,JL,MKH) and Departments of Epidemiology and Medicine, Johns Hopkins Bloomberg School of Public Health (ES), The Johns Hopkins University School of Medicine, Baltimore, Maryland

Correspondence to: Marc K. Halushka, MD, PhD, Ross Building, RM 632L, 720 Rutland Avenue, Baltimore, MD 21205. E-mail: mhalush1{at}jhmi.edu

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 m2 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. (J Histochem Cytochem 57:995–1001, 2009)

Key Words: matrix metalloproteinases • immunohistochemistry • tissue microarrays


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