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I. Maltseva, S. Rosen; The Expression of Sulf-1, a Heparan Sulfate Glucosamine 6-O-Endosulfatase, in Wounded Mouse Cornea. Invest. Ophthalmol. Vis. Sci. 2007;48(13):792.
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Wound healing is a complex process in which the behavior of cells is influenced by their interactions with the extracellular matrix (ECM) and by their responses to growth factors. Heparan sulfate proteoglycans (HSPGs) are the most abundant proteoglycans within the ECM and on the cell membrane. They act as mediators of growth factors binding and signaling. The specific structural modifications of heparan sulfate (HS) determine its role in modulating cellular responses to growth factors and morphogens. The two glucosamine 6-O-endosulfatases (Sulf-1 and Sulf-2) remove 6-O sulfate groups from trisulfated disaccharides present on heparan sulfate chains. We hypothesized that the structural modifications of HSPG chains provided by these enzymes might be an important aspect of the regulation of epithelial cell migration, proliferation, and differentiation during wound healing. Our goal was to examine the expression and functional activity of Sulf-1 during wound healing using a mouse corneal scratch model.
Five vertical and five horizontal linear scratches were applied to one cornea of male BALB/C mice with a sterile 25-gauge needle under anesthesia, while the contralateral cornea served as control. The scratches were allowed to heal for 8, 24, 48 and 72 hours. Sulf-1 and the HS trisulfated epitope were detected using immunohistochemistry.
Sulf-1 expression was restricted to the limbal epithelium in the unperturbed mouse cornea. In contrast, in wounded eyes Sulf-1 expression was detected in the corneal basal layer of the epithelium. Corneal expression of the enzyme was first detected at 8 hrs, peaked at 24 hrs and disappeared by 72 hrs. Sulf-1 expression inversely correlated with the presence of the trisulfated disaccharide epitope. Surprisingly, the decrease in the epitope was observed not only in the corneal epithelium and Bowman’s membrane (proximal to the epithelial basal cells), but also in Descemet’s membrane (distal to the epithelial layer).
Our results demonstrate differential expression and function of the HS-modifying enzyme Sulf-1 during mouse corneal injury. The induction of Sulf-1 in basal cells suggests a role for it in cell proliferation and/or differentiation during corneal regeneration.
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