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Z. Cao, N. Said, M. Garate, F. Liu, N. Panjwani; Galectins-3 and -7 Play a Role in Re-epithelialization of Corneal Wounds . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3827.
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Purpose: Disorders of corneal wound healing characterized by impaired or delayed re-epithelialization are a serious medical problem. Recent studies from our laboratory have suggested that a carbohydrate-binding protein, galectin-3, plays a role in re-epithelialization of corneal wounds. We have shown that the rate of re-epithelialization of corneal wound is perturbed in galectin-3-deficient (gal3-/-) mice and that the exogenous galectin-3 stimulates re-epithelialization of corneal wounds in gal3+/+ mice. The goal of the present study was to characterize the molecular mechanism by which galectin-3 modulates re-epithelialization of corneal wounds. Methods: BrdU in vivo labeling was used to determine whether the rate of corneal epithelial cell proliferation is perturbed in gal3-/- mice. In vitro experiments were performed to determine whether the exogenous galectin-3 stimulates re-epithelialization of corneal wounds in gal3-/- mice. Gene expression patterns of healing gal3+/+ and gal3-/- mice were compared using cDNA microarrays. Results: Quantitation of the BrdU-labeled cells in gal3+/+ and gal3-/- corneas revealed that corneal epithelial cell proliferation rate is not perturbed in gal3-/- corneas. Exogenous galectin-3 accelerated re-epithelialization of wounds in gal3+/+ mice but, surprisingly, not in the gal3-/- mice. Gene expression analysis using cDNA microarrays revealed that healing corneas of gal3-/- mice contain markedly reduced levels of another carbohydrate-binding protein, galectin-7, compared to those of gal3+/+ mice. More importantly, unlike galectin-3, galectin-7 accelerated re-epithelialization of wounds in both gal3-/- and gal3+/+ mice. The stimulatory effect was specifically inhibited by a competing disaccharide, ß-lactose. Conclusions: These findings lead us to propose that galectins-3 and –7 bind to distinct counterreceptors and that the corneas of gal3-/- mice may be deficient in the expression of the counterreceptors of the lectin itself. We further propose that galectin-3 may in fact modulate the expression of glycosyltransferases, which in turn, regulate glycosylation of the proteins which serve as cell surface or ECM counterreceptors of the lectin. Alternatively, galectin-3 may influence re-epithelialization of corneal wounds by modulating the expression of galectin-7. Regardless of the mechanisms involved, our findings that both galectins-3 and -7 stimulate re-epithelialization of corneal wounds have broad implications for developing novel therapeutic strategies for the treatment of nonhealing wounds.
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