Calcium channel inhibition accelerates polycystic kidney disease progression in the Cy/+ rat

S. Nagao, K. Nishii, D. Yoshihara, H. Kurahashi, K. Nagaoka, T. Yamashita, H. Takahashi, T. Yamaguchi, J. P. Calvet, D. P. Wallace

研究成果: ジャーナルへの寄稿学術論文査読

66 被引用数 (Scopus)


In polycystic kidney disease, abnormal epithelial cell proliferation is the main factor leading to cyst formation and kidney enlargement. Cyclic AMP (cAMP) is mitogenic in cystic but antimitogenic in normal human kidney cells, which is due to reduced steady-state intracellular calcium levels in cystic compared to the normal cells. Inhibition of intracellular calcium entry with channel blockers, such as verapamil, induced cAMP-dependent cell proliferation in normal renal cells. To determine if calcium channel blockers have a similar effect on cell proliferation in vivo, Cy/+ rats, a model of dominant polycystic kidney disease, were treated with verapamil. Kidney weight and cyst index were elevated in verapamil-treated Cy/+ rats. This was associated with increased cell proliferation and apoptosis, elevated expression, and phosphorylation of B-Raf with stimulation of the mitogen-activated protein kinase MEK/ERK (mitogen-activated protein kinase kinase/extracellular-regulated kinase) pathway. Verapamil had no effect on kidney morphology or B-Raf stimulation in wild-type rats. We conclude that treatment of Cy/+ rats with calcium channel blockers increases activity of the B-Raf/MEK/ERK pathway accelerating cyst growth in the presence of endogenous cAMP, thus exacerbating renal cystic disease.

ジャーナルKidney International
出版ステータス出版済み - 02-2008

All Science Journal Classification (ASJC) codes

  • 腎臓病学


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