Abnormal expression of epidermal growth factor and sulfated glycoprotein SGP-2 messenger RNA in a rat model of autosomal dominant polycystic kidney disease.

I t has been suggested that epithelial cells in polycystic kidney disease (PKD) exist in a developmentally immature state ( 1 ,2) as manifested by morphologic. functional, and molecular abnormalities. During normal development, renal messenger RNA (mRNA) levels for epidermal growth factor Increase (3), whereas those for the sulfated glycoprotein SGP-2 decrease ( 1 ). This process does not occur normally In animal models of autosomal recessive PKD (1.3,4). resulting in persistently low levels ofepidenmal growth factor mRNA and persistently high levels of SGP-2 mRNA. It is hypothesized that these two developmentally regulated mRNA would also be abnormally expressed in slowly progressive. autosomal dominant PKD, such as that seen In the Han:SPRD rat. In Han:SPRD rats, homozygous-cystic animals develop rapidly progressive cystic disease and die of renal failure at approximately 3 weeks of age (5). Hetenozygous animals develop cysts that enlarge over a period of months, with hetenozygous males developing prominent PKD and significant renal insufficiency by 6 months of age. and heterozygous females developing less severe PKD with minimal renal dysfunction until they reach 18 to 24 months ofage (6). This report documents abnormal expression of epidermal growth factor and sulfated glycopnotein-2 (SGP-2) mRNA in a pattern consistent with developmental immaturity of epithelial cells in this model of slowly progressive autosomal dominant PKD. Animals