Increased endothelin and endothelin receptor mRNA expression in polycystic kidneys of cpk mice

Abstract

The renal mRNA levels of endothelin (ET)-1 and ET-3 and for ET receptors A and B were measured in the cystic kidneys of cpk/cpk mice at 1, 2, and 3 wk of age. At 1 wk of age, renal ET-1 mRNA was 3.2-fold greater in cystic mice than in controls and continued to increase with the progression of cyst formation to reach 10.4-fold more than controls at 3 wk. ET-3 mRNA levels did not differ between cystic and control mice. Renal ETA and ETBreceptor mRNA increased gradually in cystic mice with the progression of their cysts, reaching 4.2- and 6.3-fold increases over controls, respectively, at 3 wk. Proliferating cell nuclear antigen mRNA expression was also examined, and proliferating cell nuclear antigen mRNA levels were found to be significantly increased in the kidneys of cystic mice compared with controls: 2.1-fold at 1 wk, 4.5-fold at 2 wk, and 7.8-fold at 3 wk. The mRNA levels for transforming growth factor β(TGF-β) and tumor necrosis factor α (TNF-α) in the kidneys of cystic mice were also examined and were found to be increased progressively with age (TGF-β, 2.1-fold at 1 wk, 4.2-fold at 2 wk, and 6.2-fold at 3 wk; TNF-a, 2.2-fold at 1 wk, 3.8-fold at 2 wk, and 5.4-fold at 3 wk). These data suggest that ET-1 and ETA and ETB receptor gene expression is up-regulated and that mRNA levels for TGF-β and TNF-α may be coordinately expressed with those for ET-1 and ET receptors in the kidneys of cpk/cpk mice.