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Tissue inhibitor of metalloproteinase 1 regulates matrix metalloproteinase activity during newt limb regeneration
Author(s) -
Stevenson Tamara J.,
Vinarsky Vladimir,
Atkinson Donald L.,
Keating Mark T.,
Odelberg Shan J.
Publication year - 2006
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20654
Subject(s) - matrix metalloproteinase , biology , regeneration (biology) , tissue inhibitor of metalloproteinase , timp1 , metalloproteinase , microbiology and biotechnology , wound healing , downregulation and upregulation , anatomy , gene expression , immunology , gene , biochemistry
Abstract Matrix metalloproteinase (MMP) activity is important for newt limb regeneration. In most biological processes that require MMP function, MMP activity is tightly controlled by a variety of mechanisms, including the coexpression of natural inhibitors. Here, we show that gene expression of one such inhibitor, tissue inhibitor of metalloproteinase 1 (NvTIMP1), is upregulated during the wound healing and dedifferentiation stages of regeneration when several MMPs are at their maximal expression levels. Newt MMPs and NvTIMP1 also exhibit similar spatial expression patterns during the early stages of limb regeneration. NvTIMP1 inhibits the proteolytic activity of regeneration‐related newt MMPs and, like human TIMP1, can induce a weak mitogenic response in certain cell types. These results suggest that NvTIMP1 may be functioning primarily to maintain optimal levels of MMP activity during the early stages of limb regeneration, while possibly serving a secondary role as a mitogen. Developmental Dynamics 235:606–616, 2006. © 2005 Wiley‐Liss, Inc.