Research topic
Bone and cartilage metabolism, Extracellular matrix, Immune Response, Infection and Inflammation, Oncology, Others, Pulmonary diseases, Renal disease
Summary
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-7 (also known as matrilysin, matrilysin 1 or pump 1; EC 3.4.24.23) has a broad range of substrate specificity including collagen type IV, elastin, fibronectin, laminin, nidogen, tenascin, osteonectin, MBP, decorin and versican). Human MMP-7 has a Mw of 29 kDa (pro-form) and 19 kDa (active form). The activity is dependent on Zn2+ and Ca2+ . proMMP-7, can be activated in vitro by organo mercurial compounds such as p-aminophenyl mercuric acetate (APMA). MMP-7 is produced by a variety of cell types including osteoclasts, keratinocytes epithelial cells and macrophages.
MMP-7 plays a crucial role in a diverse array of cellular processes and appears to be a key regulator of fibrosis in several diseases, including pulmonary fibrosis, liver fibrosis, kidney fibrosis, and cystic fibrosis. For example, MMP-7 levels are increased in patients with idiopathic pulmonary fibrosis (IPF), and research suggests that MMP-7 could potentially be a reliable prognostic marker of IPF at time of diagnosis and one that can predict the deterioration of lung function during the follow-up period. Furthermore, research has found that urinary MMP-7 levels are elevated in human chronic kidney disease (CKD) and correlate with kidney fibrosis; thus, MMP-7 could potentially serve as a noninvasive biomarker of kidney fibrosis. It was also discovered that, in mice, pharmacologic inhibition of MMP-7 attenuates renal fibrosis in vivo, suggesting that MMP-7 is a novel therapeutic target as well, and its inhibition confers renal protection against development of kidney fibrosis.
Elevated MMP-7 expression has been observed in numerous cancers. MMP-7 appears to act as an oncogene in cervical cancer cells and is involved in cell proliferation, migration, and invasion. MMP-7 expression has been found to be significantly higher in the tissue and serum of cervical cancer patients compared to healthy individuals and has been correlated with increased pathological grade, clinical stage, and lymph metastasis. This suggests that MMP-7 may be a clinically relevant biomarker for cervical cancer. Similarly, others studies have found that MMP-9 is a potential prognostic factor for ovarian cancer and could be a novel treatment target in ovarian cancer patients.
