MMP-3 polymorphism: Genetic marker in pathological processes (Review)

Abstract

Abstract. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are collectively capable of cleaving virtually all extracellular matrix (ecM) substrates and play an important role in diverse physiological and pathological processes. The activity of MMPs is controlled at multiple levels, and the transcriptional regulation of MMPs appears to represent a necessary step in its regulation. MMP-3 is a key member of the MMP family with broad substrate specificity, and is crucial to the connective tissue remodeling process. it is also involved in the turnover of the numerous ecM components. a common functional promoter polymorphism of MMP-3, 5a/6a, affects its activity and has been associated with various diseases. This polymorphism may be used as a genetic marker for certain pathologies to identify individual susceptibility. This review discusses various topics related to MMP-3 in pathological processes, with a focus on the 5a/6a polymorphism. Contents1. introduction 2. Matrix metalloproteinase-3 3. 5a/6a polymorphism of MMP-3 4. Pathological processes and the MMP-3 5a/6a polymorphism 5. Haplotype influence IntroductionThe evidence that individual characteristics play an important role in physiological and pathological processes has resulted in the targeted study of genetic polymorphisms in the clinical setting. in this context, mediators that degrade the extracellular matrix (ecM), such as matrix metalloproteinases (MMPs), are highlighted in studies involving inflammatory and degenerative diseases, and principally the prognosis and metastasis of cancer.degradation of the ecM is essential in many physiological processes, such as during development, growth and repair of tissue, and the microenvironment plays a central role in controlling both normal and transformed cell functions, as well as normal tissue integrity (1).MMPs are a pivotal family of zinc enzymes responsible for the degradation of ecM components, including basement membrane collagen, interstitial collagen, fibronectin and various proteoglycans, during normal remodeling and repair processes in development and inflammation. MMPs are also peptidase enzymes responsible for clotting factors, lipoproteins, latent growth factors and chemotactic and cell adhesion molecules (2,3). in this way, MMPs play a key role in the physiologic remodeling of tissues, including embryogenesis and tissue morphogenesis, angiogenesis, cell migration, proliferation, apoptosis, alteration of cell motility, effects on the immune system, wound repair and the inflammatory response (4).MMPs are a family of more than 25 enzymes. The expression of most MMPs is normally low in tissues and is induced when remodeling of the ecM is required. MMP gene expression is regulated primarily at the transcriptional level, but there is also evidence of the modulation of mrna stability in response to growth factors and cytokines (5). The promoter region of inducible MMP genes (i.e., MMP-3) shows remarkable conservation of regulatory elements, and their expression is induced ...

Association study of matrix metalloproteinase 3 5A/6A polymorphism with in-stent restenosis after percutaneous coronary interventions in a Han Chinese population

“…31 Therefore, MMP3 expression is suggested to have an important role in ISR formation. 19 In the current study, we found a weak association between the MMP3 5A/6A polymorphism and 6-month follow-up in ISR formation. Our data provide valuable insight to predict ISR occurrence in CAD patients after stent placement to closely follow-up and provide appropriate anti-restenosis treatment.…”

“…MMP3 (stromelysin-1), a key member of the MMP family with a broad catalyzing specificity, is particularly involved in the degradation of ECM components. 19 Thus, MMP3 is suggested to be a crucial candidate for preventing ISR formation. Atherosclerotic plaques were found to contain increased MMP3 expression and matrix degrading activity, 20 and antisense oligonucleotides to MMP3 mRNA can inhibit vascular SMC migration and proliferation.…”

Prognostic utility of TME-associated genes in pancreatic cancer

“…A previous study has confirmed that MET facilitates stromal rewiring by upregulating tenascin-C (TNC) expression, which interacts with Frontiers in Genetics frontiersin.org Frontiers in Genetics frontiersin.org 13 ECM components and is deeply involved in the metastasis of cancer, stimulating the proliferation and restraining the differentiation of CSCs in PC (Jones and Jones, 2000;Orend, 2005;Orend and Chiquet-Ehrismann, 2006;Modica et al, 2021). By proteolysis, MMP3, another high-expression gene in PC samples, destroyed various molecules, such as ECM and adhesion molecules, and enabled the tumor to be more aggressive (Sternlicht et al, 1999;Munhoz et al, 2010;Niland et al, 2021). Upregulated MMP3 participates in the progression of genomic instability in tumors (Sun et al, 2014).…”

Lack of association of matrix metalloproteinase-3 gene polymorphism with susceptibility to rheumatoid arthritis: a meta-analysis

“…In recent years, a single nucleotide polymorphism (SNP) in the promoter sequence of the MMP-3 gene have been described [ 12 – 14 ], and this polymorphism may play an important role in regulating the MMP-3 gene expression [ 15 ]. In human, the MMP-3 gene is located at the long arm of chromosome 11 (11q22.3) [ 16 ], and the promoter region of MMP-3 is characterized by 5A/6A promoter polymorphism at position of -1171(rs3025082), in which one allele has six adenosines(6A) and the second has five adenosines(5A) [ 12 ], while the 6A allele has about half the promoter strength of the 5A allele [ 15 ].…”