Elevated levels of beta defensin-1 mRNA in diabetic kidneys of GK rats.

We previously described the isolation of CDK4, representing the 3(')end of an unknown mRNA, using differential display [Biophys. Res. Commun. 232 (1997) 49]. To determine the identity of the CDK4 gene, full-length CDK4 cDNA clones were isolated from a diabetic kidney cDNA library. DNA sequencing revealed that CDK4 represents the rat beta defensin-1 gene (rBD-1). rBD-1 mRNA was detected in rat kidney, heart, lung, and skeletal muscle using RT-PCR. Using Northern blot analysis, elevated levels of the 0.5kb mRNA transcript were detected in the kidneys of 6-, 16-, 26-, and 40-week-old GK rats when compared with age-matched Wistar controls. A novel 2.0kb mRNA transcript was also detected in all kidneys examined from GK rats in none of the age-matched control kidneys. Biglycan and TGF-beta1 mRNAs were significantly up-regulated in kidneys of GK rats at 26 weeks compared to 16 and 6 weeks, showing that the kidneys of GK rats mimic the gene expression pattern described for human and experimental DN. These data suggest that overexpression of beta-defensin-1 mRNA may play a role in diabetic nephropathy.