Measures endogenous active MMP-2 ( naturally occurring ) or total active MMP-2 ( following activation with APMA ).
Samples: cell culture conditioned medium, serum, plasma, urine and tissue homogenates.
Range: 0.02 – 16 ng/ml.
Sensitivity: 0.04 ng/ml for 2 h incubation with detection reagent; 0.02 ng/ml for 6 h incubation with detection reagent; 4 pg/ml for overnight incubation
Ease-of-use: Equivalent to ELISA.
Bone and cartilage metabolism, Cardiovascular disease, Coronary artery disease, Extracellular matrix, Oncology
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for cleaving protein substrates, with the most commonly identified substrates being extracellular matrix (ECM) proteins. MMPs are involved in normal physiological processes, such embryogenesis, organogenesis during development, reproduction tissue resorption, wound healing and tissue remodeling. They also play a role in a number of pathological processes such as inflammation, arthritis, cardiovascular diseases, fibrosis and cancer.
In addition to modulating the components of the extracellular connective tissue, MMPs also regulate cell proliferation, differentiation, migration, apoptosis, and vessel regeneration indirectly by cleaving and activating vital molecules that control cell function, or directly by binding to cell surface molecules that trigger activation of intracellular pathways.
Regulation of MMPs is carried out at various levels. Expression of latent MMPs is regulated at the level of transcription, whereas the proteolytic activity is controlled by specific activation of proMMPs, and by MMP-specific inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), or general circulatory inhibitors, such as α2macroglobulin. The MMPs can be grouped according to their domain structure into collagenases, gelatinases, stromelysins, membrane type MMPs and matrilysins.
MMP-2 (also known as 72 kDa type IV collagenase, Gelatinase A; EC 18.104.22.168) degrades collagen IV, V, VII and X, as well as elastic, fibronectin, and denatured collagen type I. Human MMP-2 has a Mw of 72 kDa (proform) and 62 kDa (active form). The activity is dependent on Zn2+ and Ca2+. MMP-2 is secreted as proMMP-2, and can be activated in vitro by organo mercurial compounds such as p-aminophenyl mercuric acetate (APMA). MMP-2 is produced by a variety of cell types including fibroblasts, chondrocytes, endothelial and epithelial cells.
MMP-2 is expressed by various liver cells, most abundantly by HSCs and KCs, and is one of the widely studied enzymes in liver fibrosis. Several studies evidently correlated the expression of MMP-2 to the progression of fibrosis, regardless of the etiology (with no detectable expression in normal livers), implicating its profibrogenic properties. Increased MMP-2 expression has been associated with chronic hepatitis, liver fibrosis, alcoholic liver cirrhosis, ischemia and reperfusion injury (IRI), and biliary atresia (BA) (progressive fibroinflammatory cholangiopathy of infancy and a leading indication for pediatric liver transplantation).
The expression of MMP-2 has been strongly associated with the progression of malignancy of several types of carcinoma. In primary skin melanoma, lung carcinoma, ovarian carcinoma and brain neoplasms, the expression of the immunoreactive protein for MMP-2 was associated with a poor prognosis. In several studies, MMP-2 has been shown to be expressed in breast carcinoma and it has been localised in breast carcinoma cells using immunohistochemical methods. MMP-2 is commonly cited, along with MMP-9, for involvement in the epithelial-mesenchymal transition (EMT) process many malignant tumors, including hepatocellular carcinoma (HCC).