Galectins-3 and -7, but not Galectin-1, Play a Role in Re-epithelialization of Wounds

Abstract

Disorders of wound healing characterized by impaired or delayed re-epithelialization are a serious medical problem. These conditions affect many tissues, are painful, and are difficult to treat. In this study, using cornea as a model, we demonstrate for the first time the importance of carbohydrate-binding proteins galectins-3 and -7 in re-epithelialization of wounds. In two different models of corneal wound healing, re-epithelialization of wounds was significantly slower in galectin-3-deficient (gal3(-/-)) mice compared with wild-type (gal3(+/+)) mice. In contrast, there was no difference in corneal epithelial wound closure rates between galectin-1-deficient and wild-type mice. Quantitation of the bromodeoxyuridine-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 galectin-7 compared with those of gal3(+/+) mice. More importantly, unlike galectin-3, galectin-7 accelerated re-epithelialization of wounds in both gal3(-/-) and gal3(+/+) mice. In corresponding experiments, recombinant galectin-1 did not stimulate the corneal epithelial wound closure rate. The extent of acceleration of re-epithelialization of wounds with both galectin-3 and galectin-7 was greater than that observed in most of the published studies using growth factors. These findings have broad implications for developing novel therapeutic strategies for treating nonhealing wounds.