Role of gelatinases in pathological and physiological processes involving the dystrophin–glycoprotein complex

Abstract

Dystrophin is a cytosolic protein belonging to a membrane-spanning glycoprotein complex, called dystrophin-glycoprotein complex (DGC) that is expressed in many tissues, especially in skeletal muscle and in the nervous system. The DGC connects the cytoskeleton to the extracellular matrix and, although none of the proteins of the DGC displays kinase or phosphatase activity, it is involved in many signal transduction pathways. Mutations in some components of the DGC are linked to many forms of inherited muscular dystrophies. In particular, a mutation in the dystrophin gene, leading to a complete loss of the protein, provokes one of the most prominent muscular dystrophies, the Duchenne muscular dystrophy, which affects 1 out of 3500 newborn males. What is observed in these circumstances, is a dramatic alteration of the expression levels of a multitude of metalloproteinases (MMPs), a family of extracellular Zn(2+)-dependent endopeptidases, in particular of MMP-2 and MMP-9, also called gelatinases. Indeed, the enzymatic activity of MMP-2 and MMP-9 on dystroglycan, an important member of the DGC, plays a significant role also in physiological processes taking place in the central and peripheral nervous system. This mini-review discusses the role of MMP-2 and MMP-9, in physiological as well as pathological processes involving members of the DGC.

Glycosyltransferase POMGNT1 deficiency affects N-cadherin-mediated cell-cell adhesion

“…Since breakdown of basement membranes is also one of the hallmark events in MEB disease(11) or -dystroglycanopathy in general, elevated levels of MMPs could increase ECM protein degradation and impede cell-ECM interactions further deteriorating the clinical outcome of these patients. A similar role has been suggested for MMP2 and MMP9 in physiological and pathological conditions involving members of the dystrophin glycoprotein complex(52).…”

Silencing of gelatinase expression delays myoblast differentiation in vitro

“…Membrane MMPs also control the activation of other members of the MMP family (Bellayr et al, 2009;Bozzi et al, 2015;Snyman and Niesler, 2015). Membrane MMPs also control the activation of other members of the MMP family (Bellayr et al, 2009;Bozzi et al, 2015;Snyman and Niesler, 2015).…”

“…Stromelysins, that is, MMP-3 or MMP-10, degrade laminin, fibronectin, elastin, and the core protein of proteoglycans present in ECM surrounding muscle fibers. Membrane MMPs also control the activation of other members of the MMP family (Bellayr et al, 2009;Bozzi et al, 2015;Snyman and Niesler, 2015).…”

Matrix metalloproteinase‐9, 10, and stress hyperglycaemia in acute kidney injury

“…Our results demonstrated MMP-10 levels to be an independent predictor of the necessity of RRT and thus put forth the use of MMP-10 as a promising marker in further studies in patients with AKI. 26 Ma et al 27 showed the importance of inflammation in cardiac ageing and the role of MMP-9 in the direct and indirect polarization of the macrophages. Also, MMP-10 levels were significantly higher in patients undergoing haemodialysis than in patients in the predialysis group and were found to be a risk factor independent of atherosclerosis.…”

“…25 It also plays an important role in the degradation of extracellular matrix, activation of IL-1b, and division of some chemokines. 26 Ma et al 27 showed the importance of inflammation in cardiac ageing and the role of MMP-9 in the direct and indirect polarization of the macrophages. Bahrehmond et al 28 found a correlation between MMP-9 and systemic inflammatory markers and oxidative stress in patients with systemic lupus erythematosus.…”