Abstract
Imbalance of matrix metalloproteinases and tissue inhibitors of metalloproteinases (MMPs/TIMPs) takes part in age-related renal fibrosis; so does molecular inflammation. As several inflammatory mediators including intercellular adhesion molecule-1 (ICAM-1) are substrates of MMPs, we speculated that TIMP-1 might affect ICAM-1 through MMPs and subsequently promote age-related renal fibrosis. Then, we observed changes of kidney in human TIMP-1 transgenic mice and wild-type mice of different ages. It was found that the expressions and activities of gelatinases were downregulated; the expressions of ICAM-1, collagen III, collagen IV, and transforming growth factor (TGF)-beta1 were upregulated; and the number of infiltrating macrophages was increased in kidneys of 24-month-old TIMP-1 transgenic mice with high expressions of TIMP-1, compared with wild-type mice. Our results indicated that TIMP-1 could promote age-related renal fibrosis, which was partly attributed to enhancing inflammation through upregulation of ICAM-1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aging / physiology*
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Albuminuria
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Animals
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Collagen Type III / genetics
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Collagen Type III / metabolism
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Collagen Type IV / genetics
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Collagen Type IV / metabolism
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Creatinine / blood
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Down-Regulation / physiology
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Fibrosis
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Gene Expression
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Genotype
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Humans
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism
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Kidney / pathology*
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Macrophages / metabolism
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Matrix Metalloproteinase 2 / genetics
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism
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Mice
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Mice, Transgenic
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Models, Animal
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RNA, Messenger / metabolism
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Tissue Inhibitor of Metalloproteinase-1 / genetics
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Tissue Inhibitor of Metalloproteinase-1 / metabolism*
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Tissue Inhibitor of Metalloproteinase-2 / genetics
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Tissue Inhibitor of Metalloproteinase-2 / metabolism
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Transforming Growth Factor beta1 / genetics*
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Transforming Growth Factor beta1 / metabolism*
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Up-Regulation / physiology*
Substances
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Collagen Type III
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Collagen Type IV
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RNA, Messenger
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Tissue Inhibitor of Metalloproteinase-1
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Transforming Growth Factor beta1
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Intercellular Adhesion Molecule-1
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Tissue Inhibitor of Metalloproteinase-2
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Creatinine
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9