Matrix Metalloproteinases: A Review of Their Structure and Role in Systemic Sclerosis

Abstract

Matrix metalloproteinases (MMPs) are the main enzymes involved in arterial wall extracellular matrix (ECM) degradation and remodeling, whose activity has been involved in various normal and pathologic processes, such as inflammation, fibrosis. As a result, the MMPs have come to consider as both therapeutic targets and diagnostic tools for the treatment and diagnosis of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Systemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by an excessive over-production of collagen and other ECM, resulting in skin thickening and fibrosis of internal organs. In recent years, abnormal expression of MMPs has been demonstrated with the pathogenesis of SSc, and the association of different polymorphisms on MMPs genes with SSc has been extensively studied. This review describes the structure, function and regulation of MMPs and shortly summarizes current understanding on experimental findings, genetic associations of MMPs in SSc.

Matrix metalloproteinase gene polymorphisms and susceptibility to systemic sclerosis

“…A physiological balance between the synthesis, deposit in the extracellular environment, and degradation of these molecules is required (Robert et al, 2016). MMP enzymes degrade ECM components, promoting this required balance (Johnson et al, 2001;Peng et al, 2012). Disruption of this balance results in the fibrotic process, a pathological hallmark of SSc, which causes loss of tissue functionality and the failure of affected organs (Bhattacharyya et al, 2011;Katsumoto et al, 2011;Robert et al, 2016).…”

“…Genetic polymorphism, gene transcription, posttranslational modification, and inhibition of TIMP are all possible regulatory mechanisms of MMP (Peng et al, 2012). Thereby, the accumulation of ECM components, which results in tissue fibrosis, is not only related to polymorphisms or altered MMP gene expression, but may also be due to increase in TIMP enzyme activity, which blocks the action of MMP and inhibits matrix degradation (Murphy, 2011;Peng et al, 2012).…”

“…The fibrotic process is characterized by the deposition of extracellular matrix (ECM) proteins on normal tissue, which alters the tissue architecture and results in a loss of tissue functionality and organ failure (Bhattacharyya et al, 2011;Katsumoto et al, 2011). Matrix metalloproteinases (MMP) are enzymes that are able to degrade ECM components (Peng et al, 2012). These are involved in normal physiological processes, as well as in pathological processes such as cell proliferation, apoptosis, inflammation, aging, cancer, and arthritis (Johnson et al, 2001;Peng et al, 2012).…”

“…Matrix metalloproteinases (MMP) are enzymes that are able to degrade ECM components (Peng et al, 2012). These are involved in normal physiological processes, as well as in pathological processes such as cell proliferation, apoptosis, inflammation, aging, cancer, and arthritis (Johnson et al, 2001;Peng et al, 2012). Polymorphisms in the promoter region of MMP genes may influence gene expression and, consequently, result in an imbalance between production and degradation of ECM proteins (Peng et al, 2012).…”

“…These are involved in normal physiological processes, as well as in pathological processes such as cell proliferation, apoptosis, inflammation, aging, cancer, and arthritis (Johnson et al, 2001;Peng et al, 2012). Polymorphisms in the promoter region of MMP genes may influence gene expression and, consequently, result in an imbalance between production and degradation of ECM proteins (Peng et al, 2012). Of the polymorphisms described for MMP genes, an insertion/deletion of a guanine at MMP1 in the position -1607 results in one allele with a single guanine (1G) and another with two guanines (2G) (Johnson et al, 2001).…”