Matrix metalloproteinases in extracellular matrix remodeling: molecular, cellular and tissue aspects

Abstract

Matrix metalloproteinases are an integral component of the organ-specific tissue microenvironment, primarily participating in the regulation of the state of the integrative-buffer metabolic environment, tissue remodeling, morphogenesis and immunogenesis, and the genesis of pathological vascular diseases. Therefore, issues related to regulation of matrix metalloproteinase activity under altered gravity are a matter of high urgency for space biomedicine. The review highlights aspects of regulation of matrix metalloproteinase activity under altered gravity. The study results included in the current systematic review were searched for in independent literature sources in the PubMed and Cochrane databases, Google Scholar and the NASA Technical Reports Server. A variety of stress factors associated with space flights, in particular, exposure to radiation, enhances the expression of transforming growth factor beta and matrix metalloproteinases-2. Experimental data obtained during several flights demonstrate that microgravity affects the architecture of cells and increases the expression of matrix metalloproteinases-1 and interleukin-6. Microgravity reduces the expression of collagen I, and the level of fibrillar collagen, which affects the mechanical properties of the intracellular matrix. Matrix metalloproteinases -1, -3, -10 demonstrated an increased activity in flight samples of 16-week-old female C57BL/6J mice (n = 8) during 15 days aboard the Space Shuttle Discovery, the STS-131 mission, compared to ground control (12.94; 2.98 and 16.85 times, respectively, P<0.05), while matrix metalloproteinases inhibitors – tissue metalloproteinase inhibitors-1, -2, and -3, demonstrated no statistically significant changes in gene expression. There were determined significant differences in the gene expression profiles in the lungs of animals of the space flight and ground control groups. The genes that revealed more than doubled expression were CTGF, MMP-2, NACM1, SPARC, SPOCK1 and TIMP-3, while the genes with the greatest decrease in expression were LAMA1, MMP-3, MMP-7, MMP-13, VCAM-1, and SELE.