Role of Matrix Metalloproteinases 2 and 9 in Lacrimal Gland Disease in Animal Models of Sjögren's Syndrome
| Autor: | Paul C. Leavis, Mahta Samizadeh, William M. Thomas, Helene Armaos, Hema S. Aluri, Dillon Hawley, Driss Zoukhri, Helen P. Makarenkova, Claire L. Kublin, Suharika Thotakura |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Pathology Mice Inbred MRL lpr Blotting Western Lacrimal gland Matrix metalloproteinase Biology Lacrimal apparatus Real-Time Polymerase Chain Reaction Extracellular matrix Cornea Mice Mice Inbred NOD Internal medicine medicine Animals Zymography skin and connective tissue diseases NOD mice Mice Inbred BALB C Lacrimal Apparatus Immunohistochemistry Disease Models Animal medicine.anatomical_structure Endocrinology Sjogren's Syndrome Gene Expression Regulation Matrix Metalloproteinase 9 Tears Matrix Metalloproteinase 2 RNA Female |
| Zdroj: | Investigative ophthalmologyvisual science. 56(9) |
| ISSN: | 1552-5783 |
| Popis: | Purpose Chronic inflammation of the lacrimal gland results in changes in the composition of the extracellular matrix (ECM), which is believed to compromise tissue repair. We hypothesized that increased production/activity of matrix metalloproteinases (MMPs), especially MMP-2 and -9, in inflamed lacrimal glands modifies the ECM environment, therefore disrupting tissue repair. Methods The lacrimal glands from female MRL/lpr and male NOD mice along with their respective control strains were harvested and divided into three pieces and processed for histology, immunohistochemistry, zymography, Western blotting, and RNA analyses. In another study, MRL/lpr mice were treated for 5 weeks with a selective MMP2/9 inhibitor peptide or a control peptide. At the end of treatment, the lacrimal glands were excised and the tissue was processed as described above. Results There was a 2.5- and 2.7-fold increase in MMP2 gene expression levels in MRL/lpr and NOD mice, respectively. Matrix metalloproteinase 2 and 9 enzymatic activities and protein expression levels were significantly upregulated in the lacrimal glands of MRL/lpr and NOD mice compared to controls. Treatment with the MMP2/9 inhibitor resulted in decreased activity of MMP-2 and -9 both in vitro and in vivo. Importantly, MMP2/9 inhibitor treatment of MRL/lpr mice improved aqueous tear production and resulted in reduced number and size of lymphocytic foci in diseased lacrimal glands. Conclusions We conclude that MMP2/9 expression and activity are elevated in lacrimal glands of two murine models of Sjogren's syndrome, suggesting that manipulation of MMP2/9 activity might be a potential therapeutic target in chronically inflamed lacrimal glands. |
| Databáze: | OpenAIRE |
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