Polycystic kidney disease in Han:SPRD Cy rats is associated with elevated expression and mislocalization of SamCystin

Shizuko Nagao, Miwa Morita, Masanori Kugita, Daisuke Yoshihara, Tamio Yamaguchi, Hiroki Kurahashi, James P. Calvet, Darren P. Wallace

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Polycystic kidney disease (PKD) in Han:SPRD Cy rats is caused by a missense mutation in Anks6 (also called Pkdr1), leading to an R823W substitution in SamCystin, a protein that contains ankyrin repeats and a sterile alpha motif (SAM). The cellular function of SamCystin and the role of the Cy (R823W) mutation in cyst formation are unknown. In normal SPRD rats, SamCystin was found to be expressed in proximal tubules and glomeruli; protein expression was highest at 7 days of age and declined by ∼50-60% at 45-84 days of age. In Cy/+ and Cy/Cy kidneys, expression of SamCystin was lower than in +/+ kidneys at 3 and 7 days but became elevated at 21 days. Immunohistochemical analysis revealed that SamCystin was distributed on the brush border of proximal tubules in normal rat kidneys. In Cy/+ kidneys, there were robust SamCystin staining in cyst-lining epithelial cells and loss of apical localization, and increased number of PCNA-positive cells in cyst-lining epithelia. Verapamil, an L-type Ca2+ channel blocker, accelerated PKD progression in this model and caused a further increase in the expression and abnormal distribution of SamCystin. We conclude that aberrant expression and mislocalization of R823W SamCystin lead to increased cell proliferation and renal cyst formation.

Original languageEnglish
Pages (from-to)F1078-F1086
JournalAmerican Journal of Physiology - Renal Physiology
Volume299
Issue number5
DOIs
Publication statusPublished - 01-11-2010

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

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