Detection of differentially expressed wound-healing-related glycogenes in galectin-3-deficient mice

A prior study showed that exogenous galectin-3 (Gal-3) stimulates re-epithelialization of corneal wounds in wild-type (Gal-3(+/+)) mice but, surprisingly, not in galectin-3-deficient (Gal-3(-/-)) mice. In an effort to understand why the injured corneas of Gal-3(-/-) mice are unresponsive to exogenous Gal-3, the present study was designed to determine whether genes encoding the enzymes that regulate the synthesis of glycan ligands of Gal-3 are differentially expressed in Gal-3(-/-) corneas compared with the Gal-3(+/+) corneas.

Glycogene microarray technology was used to identify differentially expressed glycosyltransferases in healing Gal-3(+/+) and Gal-3(-/-) corneas.

Of approximately 2000 glycogenes on the array, the expression of 8 was upregulated and that of 14 was downregulated more than 1.3-fold in healing Gal-3(-/-) corneas. A galactosyltransferase, beta3GalT5, which has the ability to synthesize Gal-3 ligands was markedly downregulated in healing Gal-3(-/-) corneas. The genes for polypeptide galactosaminyltransferases (ppGalNAcT-3 and -7) that are known to initiate O-linked glycosylation and N-aspartyl-beta-glucosaminidase, which participates in the removal of N-glycans, were found to be upregulated in healing Gal-3(-/-) corneas. Microarray data were validated by qRT-PCR.

Based on the known functions of the differentially expressed glycogenes, it appears that the glycan structures on glycoproteins and glycolipids, synthesized as a result of the differential glycogene expression pattern in healing Gal-3(-/-) corneas may lead to the downregulation of specific counterreceptors for Gal-3. This may explain, at least in part, why, unlike healing Gal-3(+/+) corneas, the healing Gal-3(-/-) corneas are unresponsive to the stimulatory effect of exogenous Gal-3 on re-epithelialization of corneal wounds.