Biological or Clinical Significance:
Matrix MetalloProteinases (MMPs) are zinc-dependent endopeptidases that catalyze degradation of extracellular matrix proteins, thereby controlling such processes as development, tissue remodeling, wound healing and tumor metastasis. The activity of MMPs is controlled by regulation of expression and secretion, by proteolytic activation of pro-enzymes and by the Tissue Inhibitors of MetalloProteinases (TIMPs).
TIMP-1 is a 184 amino-acid residue glycosylated protein.
TIMP-1 is widely synthesized by many cells and tissues. Many physiological functions of TIMP-1 are closely tied to the functions of MMPs, and an improper balance of MMP and TIMP production correlates with pathological conditions such as arthritis, tumor growth and metastasis. On the other hand, TIMP-1 was independently discovered as an erythroid potentiating activity, an activity that appears to be functionally distinct from MMP inhibitory activity. TIMP-1 binds to certain cell lines and is translocated to the nucleus. It inhibits apoptosis in B-cells, further suggesting that TIMP-1 independently functions in multiple ways to support survival and growth of cells in contrast to its function of inhibition MMP.
Principle of Test Method:
The TIMP-1 assay is a solid-phase ELISA that employs the quantitative sandwich enzyme immunoassay principle.
Jung K, Nowak L, Lein M, Henke W, Schnorr D, Loening S. What kind of specimen should be selected for determining tissue inhibitor of metalloproteinase-1 (TIMP-1)in blood?. Clin Chim Acta. 1996; 254: 97-100.
Jung K, Nowak L, Lein M, Henke W, Schnorr W, Loening S. Role of specimen collection in preanalytical variation of metalloproteinases and their inhibitors. Clin Chem. 1996; 42:2043-2045.
Lomholt AF, Frederiksen CB, Christensen IJ, Brünner N, Nielsen HJ. Plasma tissue inhibitor of metalloproteinases-1 as a biological marker? Pre-analytical considerations. Clin Chim Acta. 2007; 380:128-132.
Plumpton T, Clark IM, Plumpton C, Calvin J, Cawston TE. Development of an enzyme-linked immunosorbent assay to measure total TIMP-1 (Free TIMP-1 and TIMP-1 in combination with matrix-metalloproteinases) and measurement of TIMP 1 and CRP in serum. Clin Chim Acta 1995, 240: 137-154.