RNA‐Seq analysis of glycosylation related gene expression in Streptozotocin‐induced diabetic rat kidney inner medulla

Abstract

The UT‐A1 urea transporter plays an important role in the urinary concentration mechanism. Native UT‐A1 from kidney inner medulla (IM) is a heavily glycosylated protein with two glycoforms of 97 and 117 kDa. In diabetes, the protein abundance, particularly of the 117 kD isoform, is significantly increased, corresponding to an increased urea permeability in perfused IMCDs. In this study, by using sugar‐specific binding lectins, we found that the UT‐A1 glycan structure was also dramatically changed under diabetic conditions. UT‐A1 became highly sialyated, fucosylated, and branched. These changes were also accompanied by an alteration of UT‐A1 association with galectin proteins, a group of â‐galactoside glycan binding proteins. To explore the molecular basis of alterations in glycan structures, we then sought to employ the next generation sequencing (NGS) technology Illumina RNA‐Seq to identify genes involved in the process of UT‐A1 glycosylation in the IM tip of streptozotocininduced diabetic rat kidney. We found that the sialylation enzymes, glycosyltransferase Mgat, and galectin were upregulated. In contrast, the fucosylation enzyme Fut8 was downregulated under diabetic conditions. The change of these glycosylation related genes may play an important role in changing UT‐A1 glycan structure, and therefore regulate kidney urea transport activity under diabetic conditions.