Tissue inhibitor of metalloproteinase 1 regulates matrix metalloproteinase activity during newt limb regeneration.
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.
Stevenson
Tamara J
TJ
Department of Internal Medicine, Division of Cardiology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
Vinarsky
Vladimir
V
Atkinson
Donald L
DL
Keating
Mark T
MT
Odelberg
Shannon J
SJ
D000595:Amino Acid Sequence; D000818:Animals; D005121:Extremities / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D045726:Metalloproteases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008969:Molecular Sequence Data; D012038:Regeneration / Q000235:genetics; D012455:Salamandridae / Q000378:metabolism / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014945:Wound Healing / Q000235:genetics
D019715:Tissue Inhibitor of Metalloproteinase-1; D045726:Metalloproteases