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T. Blanco, X. Q. Guo, A. E. K. Hutcheon, J. D. Zieske; Role of Beta-6 Integrin and Thrombospondin-1 in the Restoration of Epithelial Basement Membrane. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6299.
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Transforming Growth Factor-Beta (TGF-β) has been shown to play a main role in stromal fibrosis after corneal injury. Disruption of the epithelial basement membrane integrity appears to be a main trigger for TGF-β release into the corneal stroma. We have previously shown that two local activators of TGF-β_thrombospondin-1 (TSP-1) and integrin Beta 6 (β6)_are upregulated during corneal wound repair. The aim of this work was to evaluate the role of both β6 and TSP-1 in restoring the epithelial basement membrane after superficial keratectomy in a mouse wound model.
One-mm superficial keratectomy wounds were made in 129 SVE wild type mice (WT), β6 null mice, TSP-1 null mice and β6-TSP-1 double null mice. The wound was allowed to heal for up to 8 weeks. Indirect immunofluorescence was used to evaluate the pattern of basement membrane restoration by means of laminin expression, and to evaluate the expression of TSP-1 in a wound-healing cornea.
A delay in the full restoration of basement membrane was observed in the TSP-1 (4 week) with respect to WT mice (2 weeks). Interestingly, the basement membrane was not restored in either the β6 or β6-TSP-1 mice by 8 weeks. In the control eyes, laminin appears as a continuous line subjacent to the epithelium. Expression of TSP-1 was observed within the wound area under the epithelium in the WT mice (day 2-week 2), β6 (day 2-week 8). TSP-1 expression was not found in the TSP-1 and β6-TSP-1 deficient mice, and in unwounded eyes.
β6 appears to be essential in the correct assembly of the basement membrane after injury. TSP-1 may play a role in basement membrane restoration by inducing expression of laminin. How TSP-1 and β6 affect the release and activation of TGF-β is a subject for our further studies.
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