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Alterations in matrix metalloproteinase‐9 levels and tissue inhibitor of matrix metalloproteinases‐1 expression in a transforming growth factor‐β transgenic model of hydrocephalus
Author(s) -
Zechel Jennifer,
Gohil Harsh,
Lust W. David,
Cohen Alan
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10326
Subject(s) - matrix metalloproteinase , transgene , extracellular matrix , transforming growth factor , biology , genetically modified mouse , tissue inhibitor of metalloproteinase , growth factor , microbiology and biotechnology , transforming growth factor beta , immunohistochemistry , endocrinology , immunology , biochemistry , receptor , gene
The development of spontaneous hydrocephalus in mouse models resulting from the overexpression of transforming growth factor‐β (TGFβ‐1) has been previously described, although the mechanism by which this occurs remains obscure. It has been previously demonstrated that increased expression of TGFβ has consequences for the levels of matrix metalloproteinases (MMPs) and their specific inhibitors (tissue inhibitors of MMPs, or TIMPs). These remodeling proteins play an important role in extracellular matrix (ECM) maintenance through degradation and deposition of ECM components. The present study investigated the relationship between elevated levels of TGFβ‐1, the ECM modulators TIMP‐1 and MMP‐9, and development of hydrocephalus in the neonatal mouse. In newborn pups, TIMP‐1 mRNA levels were equal between animals expressing the TGFβ‐1 transgene and littermates without the transgene. However, immunohistochemistry of littermate pups shows that the distribution of TIMP‐1 was changed from homogeneous with large punctate concentrations of signal to uniform, dense staining in hydrocephalic animals carrying the TGFβ‐1 transgene. The mRNA levels of MMP‐9 were decreased in the transgenic animals, as were the activity levels MMP‐9. These results suggest that the remodeling protein MMP‐9 and its specific inhibitor, TIMP‐1, may contribute to the spontaneous development of hydrocephalus in this transgenic model by altering the ECM environment. © 2002 Wiley‐Liss, Inc.