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Elizabeth A. Berger, Kerry Vistisen, Ronald P. Barrett, Linda D. Hazlett; Vasoactive Intestinal Peptide Modulates ECM Restoration and Promotes Healing after Pseudomonas aeruginosa-Induced Corneal Infection. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5820.
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© ARVO (1962-2015); The Authors (2016-present)
Studies from our laboratory have demonstrated that vasoactive intestinal peptide (VIP) directly converts the normally susceptible C57/BL/6 (B6) mouse to resistant after P. aeruginosa induced keratitis. Previously, we have shown that VIP regulates cytokine/chemokine production, host inflammatory cell function, adhesion molecule expression and Toll-like receptors (TLRs) and TLR-related molecules, ultimately modulating the inflammatory response. This study examines mechanisms by which VIP influences the healing phase following corneal infection; specifically reconstitution of the extracellular matrix.
B6 mice received daily i.p. injections of VIP from -1 through 7 days p.i. Control mice were similarly injected with PBS. Real-time RT-PCR, ELISA and immunohistochemistry (IHC) were used to assess the effects of VIP treatment on ECM reconstitution. In vitro stimulation assays were performed using B6-derived fibroblasts to test the effects of VIP treatment using the aforementioned techniques.
VIP treatment resulted in disparate expression of ECM components when compared to PBS-treated controls. Analysis revealed that corneas of VIP-treated mice had significantly increased levels for CD44, ITG-α1, ITG-α2, laminin-α1, laminin-γ1, and versican; while others such as COL5A1, COL6A1, COL12A1, COL15A1, ITG-α6, secreted phosphoprotein 1, and extracellular matrix protein 1 were significantly down-regulated when compared to PBS-treated animals.
VIP treatment down-regulates the expression of molecules associated with the degradation of the matrix, while up-regulating the production of those molecules known to enhance ECM reconstitution and function. In addition, VIP stimulates fibroblasts to express molecules associated with healing. The data from this study suggest that VIP not only in regulates disease pathogenesis, but also functions to restore integrity of the corneal stroma.
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