Epithelial-to-mesenchymal transition in cyst lining epithelial cells in an orthologous PCK rat model of autosomal-recessive polycystic kidney disease

Hiroko Togawa, Koichi Nakanishi, Hironobu Mukaiyama, Taketsugu Hama, Yuko Shima, Mayumi Sako, Masayasu Miyajima, Kandai Nozu, Kazuhiro Nishii, Shizuko Nagao, Hisahide Takahashi, Kazumoto Iijima, Norishige Yoshikawa

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Abstract

In polycystic kidney disease (PKD), cyst lining cells show polarity abnormalities. Recent studies have demonstrated loss of cell contact in cyst cells, suggesting induction of epithelial-to-mesenchymal transition (EMT). Recently, EMT has been implicated in the pathogenesis of PKD. To explore further evidence of EMT in PKD, we examined age- and segment-specific expression of adhesion molecules and mesenchymal markers in PCK rats, an orthologous model of human autosomal-recessive PKD. Kidneys from 5 male PCK and 5 control rats each at 0 days, 1, 3, 10, and 14 wk, and 4 mo of age were serially sectioned and stained with segment-specific markers and antibodies against E-cadherin, Snail1, β-catenin, and N-cadherin. mRNAs for E-cadherin and Snail1 were quantified by real-time PCR. Vimentin, fibronectin, and α-smooth muscle actin (α-SMA) expressions were assessed as mesenchymal markers. E-cadherin expression pattern was correlated with the disease pathology in that tubule segments showing the highest expression in control had much severer cyst formation in PCK rats. In PCK rats, E-cadherin and β-catenin in cystic tubules was attenuated and localized to lateral areas of cell-cell contact, whereas nuclear expression of Snail1 increased in parallel with cyst enlargement. Some epithelial cells in large cysts derived from these segments, especially in adjacent fibrotic areas, showed positive immunoreactivity for vimentin and fibronectin. In conclusion, these findings suggest that epithelial cells in cysts acquire mesenchymal features in response to cyst enlargement and participate in progressive renal fibrosis. Our study clarified the nephron segment-specific cyst profile related to EMT in PCK rats. EMT may play a key role in polycystic kidney disease.

Original languageEnglish
Pages (from-to)F511-F520
JournalAmerican Journal of Physiology - Renal Physiology
Volume300
Issue number2
DOIs
Publication statusPublished - 01-02-2011

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Togawa, H., Nakanishi, K., Mukaiyama, H., Hama, T., Shima, Y., Sako, M., Miyajima, M., Nozu, K., Nishii, K., Nagao, S., Takahashi, H., Iijima, K., & Yoshikawa, N. (2011). Epithelial-to-mesenchymal transition in cyst lining epithelial cells in an orthologous PCK rat model of autosomal-recessive polycystic kidney disease. American Journal of Physiology - Renal Physiology, 300(2), F511-F520. https://doi.org/10.1152/ajprenal.00038.2010