Journal of Histochemistry and Cytochemistry
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Originally published as JHC exPRESS on October 27, 2008.
doi:10.1369/jhc.2008.952531
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Journal of Histochemistry and Cytochemistry
Volume 57 (3): 207-213, 2009
Copyright ©The Histochemical Society, Inc.

Tissue Inhibitor of Matrix Metalloproteinase-3 Levels in the Extracellular Matrix of Lung, Kidney, and Eye Increase With Age

Anne M. Macgregor, Charles G. Eberhart, Mostafa Fraig, Jie Lu and Marc K. Halushka

Department of Pathology (AMM,CGE,MF,JL,MKH) and Department of Ophthalmology (CGE), 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

Tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) is an important regulator of matrix metalloproteinase activity in many types of disease, including atherosclerosis, neoplasia, and inflammatory conditions. Among TIMPs, TIMP-3 uniquely binds the extracellular matrix (ECM). We performed IHC staining on 17 tissue microarrays containing >1500 samples to determine the location of ECM TIMP-3 staining in a variety of predominantly vascular tissues. We found a unique pattern of TIMP-3 staining in the ECM of renal arterioles, small pulmonary vessels and parenchyma, and Bruch's membrane in the retina. There was no staining in larger caliber arteries including coronary and internal mammary arteries. TIMP-3 protein accumulation was found to be an age-dependent phenomenon, with staining appearing in all three tissues in early adulthood and becoming more robust among the elderly. These findings may help to explain the late onset of the TIMP-3–associated ocular diseases Sorsby fundus dystrophy and age-related macular degeneration and suggest a similar phenomenon could be at work in other age-related conditions. (J Histochem Cytochem 57:207–213, 2009)

Key Words: tissue inhibitor of matrix metalloproteinase-3 • extracellular matrix • immunohistochemistry


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T. C. Cornish, S. M. Bagnasco, A. M. Macgregor, J. Lu, E. Selvin, and M. K. Halushka
Glomerular Protein Levels of Matrix Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinase-1 Are Lower in Diabetic Subjects
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[Abstract] [Full Text] [PDF]



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