Glucose regulation of CDK7, a putative thiol related gene, in experimental diabetic nephropathy

We previously described the identification of the 3'end of an unknown gene CDK7 using differential display which appeared to be up-regulated in diabetic kidneys [R.A. Page, C.A. Morris, J.D. Williams, C.J. von Ruhland, A.N. Malik, Isolation of diabetes-associated kidney genes using differential display, Biochem. Biophys. Res. Commun. 232 (1997) 49-53]. Here we show that CDK7 is a putative thiol related gene which is regulated by glucose in human and rat renal cells. CDK7 mRNA increased by >threefold in cultured human mesangial cells grown in high glucose for 4 days. In the kidneys of the GK rat, a model of type II diabetes, CDK7 showed a steady age-related increase in mRNA, increasing to >sixfold in 40 week GK rats compared to normoglycemic age-matched Wistar rat kidneys, this increase correlates with progressive hyperglycemia. CDK7 mRNA is widely expressed, showing particularly high levels of expression in rat and human liver, and encodes a putative 338 amino acids highly conserved peptide with several conserved domains, including a cys-pro-arg-cys domain conserved in 15 diverse species which is similar to the catalytic centre of thioredoxin, suggesting a role in oxidative stress.