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      Correlation between Tissue Characterization and Dynamic Expression of Matrix Metalloproteinase-2 and Its Tissue Inhibitor in Conjunctival Filtering Bleb of Rats

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      1 , , 1 , 2 , 3
      BioMed Research International
      Hindawi

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          Abstract

          Purpose

          Using rat conjunctival bleb model, we correlated changes morphology and histology in the bleb with changes in MMP-2 and TIMP-2 levels.

          Methods

          Filtering surgeries were performed on rats. Dynamic changes in morphology and histopathology were observed using HE staining. Expression of MMP-2 and TIMP-2 was determined by immunofluorescence microscopy and western blotting.

          Results

          Well-elevated filtering blebs formed and persisted for an average of 12 days. Histological examination showed that inflammatory was dominant in postoperative days 1–3, and proliferating manifestation became the main sign 5 days later. Western blot showed that MMP-2 was downregulated 1 day after surgery, upregulated at 3 days, and observed with a peak at 7 days; then it persisted until 28 days. The difference was statistically significant ( F = 280.18, p < 0.01).TIMP-2 was upregulated 1 day after surgery and observed with a peak at 5 days; then it persisted until 28 days. The difference was statistically significant ( F = 145.34, p < 0.01).

          Conclusions

          During the processes of conjunctival filtering bleb and scar formation in rats, the changes in MMP-2 and TIMP-2 levels in the filtering area, together with a corresponding proliferation of fibroblasts and the accumulation of collagen fibres, resulted in scarring of filtering blebs.

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          Most cited references26

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          Matrix metalloproteinases and their inhibitors in connective tissue remodeling.

          Matrix metalloproteinases are an important group of zinc enzymes responsible for degradation of the extracellular matrix components such as collagen and proteoglycans in normal embryogenesis and remodeling and in many disease processes such as arthritis, cancer, periodontitis, and osteoporosis. A matrixin family is defined, comprising at least seven members that range in size from Mr 28,000 to 92,000 and are related in gene sequence to collagenase. All family members are secreted as zymogens that lose peptides of about 10,000 daltons upon activation. Latency is due to a conserved cysteine that binds to zinc at the active center. Latency is overcome by physical (chaotropic agents), chemical (HOCl, mercurials), and enzymatic (trypsin, plasmin) treatments that separate the cysteine residue from the zinc. Expression of the metalloproteinases is switched on by a variety of agents acting through regulatory elements of the gene, particularly the AP-1 binding site. A family of protein inhibitors of Mr 28,500 or less binds strongly and stoichiometrically in noncovalent fashion to inhibit members of the family. The serum protein alpha 2-macroglobulin and relatives are also strongly inhibitory.
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            Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion.

            Cells adhere to one another and/or to matrices that surround them. Regulation of cell-cell (intercellular) and cell-matrix adhesion is tightly controlled in normal cells, however, defects in cell adhesion are common in the majority of human cancers. Multilateral communication among tumor cells with the extracellular matrix (ECM) and neighbor cells is accomplished through adhesion molecules, ECM components, proteolytic enzymes and their endogenous inhibitors. There is sufficient evidence to suggest that reduced adherence is a tumor cell property engaged during tumor progression. Tumor cells acquire the ability to change shape, detach and easily move through spaces disorganizing the normal tissue architecture. This property is due to changes in expression levels of adhesion molecules and/or due to elevated levels of secreted proteolytic enzymes, including matrix metalloproteinases (MMPs). Among other roles, MMPs degrade the ECM and, therefore, prepare the path for tumor cells to migrate, invade and spread to distant secondary areas, where they form metastasis. Tissue inhibitors of metalloproteinases or TIMPs control MMP activities and, therefore, minimize matrix degradation. Both MMPs and TIMPs are involved in tissue remodeling and decisively regulate tumor cell progression including tumor angiogenesis. In this review, we describe and discuss data that support the important role of MMPs and TIMPs in cancer cell adhesion and tumor progression. Published by Elsevier Ltd.
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              • Record: found
              • Abstract: not found
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              Trabeculectomy, risk factors for failure and the preoperative state of the conjunctiva.

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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2017
                18 September 2017
                : 2017
                : 1054129
                Affiliations
                1Department of Ophthalmology, Affiliated Hospital of Qingdao University, Qingdao, China
                2Department of Ophthalmology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
                3Central Laboratory, Affiliated Hospital of Qingdao University, Qingdao, China
                Author notes

                Academic Editor: Ilias Georgalas

                Author information
                http://orcid.org/0000-0003-1736-7880
                http://orcid.org/0000-0002-7676-3181
                Article
                10.1155/2017/1054129
                5624151
                cf7eb2bb-223d-4062-a7f8-0ad9f3939e37
                Copyright © 2017 Ling Wang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 March 2017
                : 2 July 2017
                : 6 August 2017
                Funding
                Funded by: China Shandong Province Outstanding Young Scientist
                Award ID: BS2010SW008
                Categories
                Research Article

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