Unbalanced expression of tissue inhibitors of metalloproteinases (TIMP) such as TIMP-1 relative to matrix metalloproteinases (MMPs) promotes progression of fibrosis in liver, lung, and kidney. As to therapeutic strategies, it would be advantageous to antagonize TIMP-1. MMP-9 binds TIMP-1 with high affinity (Ki < 50 pM). Three histidine residues constitute the active site of the enzyme by bindin...

We have used adenovirus-mediated gene delivery of tissue inhibitor of metalloproteinase (TIMP)-1, -2, and -3 to examine their effect on the invasion capacity of metastatic melanoma cell lines SK-Mel-5 and A2058. Infection of melanoma cells with recombinant replication-deficient adenoviruses coding for TIMP-1, TIMP-2, and TIMP-3 resulted in marked secretion of TIMP-1 and TIMP-2 to culture medium...

BACKGROUND To clarify whether circulating matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) can be used as serum markers of fibroproliferation in chronic liver diseases, we studied the expression of MMP-2 and MMP-9 in relation to TIMP-1 and TIMP-2 in peripheral blood mononuclear leukocytes (MNLs) and polymorphonuclear leukocytes (PMLs), and compared this expression to circula...

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a widely secreted protein that regulates cell motility, proliferation, and apoptosis. Although it is recognized that TIMP-1-tetraspanin CD63 regulates epithelial cell apoptosis and proliferation, how TIMP-1 controls cell motility is not well understood. In this study, we identify tetraspanin CD82 (also called KAI1) as a component of the promi...

PURPOSE Tissue inhibitors of metalloproteinases (TIMP) are capable of inhibiting the matrix metalloproteinases, but they also possess other biological functions. Little is known about the role of TIMP-1 in the progression and spreading of cancer cells among patients with head and neck squamous cell carcinoma (HNSCC). In this study, the pretreatment serum levels of TIMP-1 or the overexpression o...

Tissue inhibitor of metalloproteinases-1 (TIMP-1) regulates matrix metalloproteinase activity, acts as a growth stimulator and inhibits apoptosis. We developed transgenic mice to evaluate the relevance of circulating versus mammary TIMP-1 in mammary carcinogenesis. The transgene was placed under the control of the albumin (Alb) promoter for the production of large amounts of TIMP-1 in the liver...

Elevated tissue inhibitor of metalloproteinase (TIMP)-1 expression contributes to excess production of extracellular matrix in liver fibrosis. However, there are few studies on sustained suppression of TIMP-1. We aimed to construct a recombinant adeno-associated virus (AAV) carrying small interfering RNAs (siRNAs) of TIMP-1 and investigate the long-term effects of RNA interference upon the TIMP...

The antiangiogenic function of the tissue inhibitors of metalloproteinases (TIMPs) has been attributed to their matrix metalloproteinase inhibitory activity. Here we demonstrate that TIMP-1 but not Ala TIMP-1 inhibits both basal and vascular endothelial growth factor (VEGF)-stimulated migration of human microvascular endothelial cells (hMVECs), suggesting that this effect is dependent on direct...

OBJECTIVE We have recently demonstrated that endothelial nitric oxide synthase (eNOS) promotes cardiomyocyte proliferation. However, mechanisms by which eNOS regulates cardiomyocyte proliferation are not fully understood. The goal of the present study was to investigate the role of tissue inhibitor of metalloproteinase-3 (TIMP-3) in eNOS-mediated cardiomyocyte proliferation. METHODS AND RESUL...

Recent studies have directed the interests at modulating the heart failure process through inhibition of activated MMPs. We hypothesized that a loss of MMP inhibitory control by TIMP-1 deficiency alters the course of post-infarction chamber remodeling and induced chronic myocardial infarction in wild-type and TIMP-1-/-mice. LV pressure-volume loops obtained from wild-type and TIMP-1-/-mice demo...