Regulation of matrix metalloproteinase activity in health and disease

Abstract

The activity of matrix metalloproteinases (MMPs) is regulated at several levels, including enzyme activation, inhibition, complex formation and compartmentalization. Regulation at the transcriptional level is also important, although this is not a subject of the present minireview. Most MMPs are secreted and have their function in the extracellular environment. This is also the case for the membrane‐type MMPs (MT‐MMPs). MMPs are also found inside cells, both in the nucleus, cytosol and organelles. The role of intracellular located MMPs is still poorly understood, although recent studies have unraveled some of their functions. The localization, activation and activity of MMPs are regulated by their interactions with other proteins, proteoglycan core proteins and/or their glycosaminoglycan chains, as well as other molecules. Complexes formed between MMPs and various molecules may also include interactions with noncatalytic sites. Such exosites are regions involved in substrate processing, localized outside the active site, and are potential binding sites of specific MMP inhibitors. Knowledge about regulation of MMP activity is essential for understanding various physiological processes and pathogenesis of diseases, as well as for the development of new MMP targeting drugs.

Zinc and metalloproteinases 2 and 9: What is their relation with breast cancer?

“…In the first case, it promotes the proliferation of neoplastic cells and metastatic dissemination through the degradation of the extracellular matrix and basal membrane, while indirectly it promotes angiogenesis, providing nutrition and dissemination of the tumor. 14 The first evidence of the involvement of MMPs in cancer came from studies in animal models. Experiments with tumor cells in mice showed that benign tumor cells acquire malignant properties when there is increased expression of these enzymes.…”

Resistance exercise recovers the structure of cartilage and synovial membrane of the ankle joint of rats after sciatic compression

“…According to Kojima, Hoso, Watanabe, Matsuzaki, Hibino, Sasaki 46 , these changes may be related to the presence of flocculation, corrosion and cracks in the articular cartilage. Taking into consideration the findings of studies by Hadler-Olsen, Fadnes, Sylte, Uhlin-Hansen, Winberg 47 and Takaishi, Kimura, Dalah, Okada, D'Armiento 48 , the changes that were observed in the present study in the LG and EG may have been the result of an increase in the rate of synthesis and the secretion of matrix-degrading enzymes by chondrocytes, as well as the production of metalloproteases that are capable of unfolding collagen and proteoglycans, which release their fragments in the articular fluid, thereby weakening the cartilage matrix. Synovial fluid and the fibrous articular capsule respond to these fragments and other biochemical mediators, such as cytokines and leukotrienes, which leads to changes in the other components of the joint.…”

Furin as proprotein convertase and its role in normal and pathological biological processes

“…Они запускают гидролиз фибриллярных коллагенов, которые составляют основу соединительнотканного барьера при развитии деструктивных инвазивных процессов, а также участвуют в гидролизе коллагена базальных мембран (через ММП-2), способствуя метастазированию [40][41][42]. В настоящее время у человека известно шесть МТ-ММП [37,43]. Наиболее изученной является МТ1-ММП (рис.…”

“…Однако этот фермент непосредственно не гидролизует коллаген IV типа, основу базальных мембран, но он активирует проММП-2, которая гидролизует коллаген IV типа и обеспечивает развитие метастатического процесса [44][45][46]. МТ1-ММП отвечает за активацию и проММП-13 (коллагеназы 3), которая обладает широкой субстратной специфичностью, гидролизует фибриллярные коллагены, коллаген IV типа и целый ряд компонентов СТМ, принимает участие в развитии онкологических поцессов [43,46,47]. Механизм активации этого фермента неизвестен [24].…”