Tissue inhibitor of metalloproteinase 1 regulates matrix metalloproteinase activity during newt limb regeneration
Article first published online: 21 DEC 2005
Copyright © 2005 Wiley-Liss, Inc.
Volume 235, Issue 3, pages 606–616, March 2006
How to Cite
Stevenson, T. J., Vinarsky, V., Atkinson, D. L., Keating, M. T. and Odelberg, S. J. (2006), Tissue inhibitor of metalloproteinase 1 regulates matrix metalloproteinase activity during newt limb regeneration. Dev. Dyn., 235: 606–616. doi: 10.1002/dvdy.20654
- Issue published online: 7 FEB 2006
- Article first published online: 21 DEC 2005
- Manuscript Accepted: 4 NOV 2005
- National Institute of Neurological Disorders and Stroke. Grant Number: NS43878
- tissue inhibitor of metalloproteinase 1;
- limb regeneration;
- matrix metalloproteinases;
- Notophthalmus viridescens
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.