Prorenin receptor is essential for normal podocyte structure and function

Yoichi Oshima, Kenichiro Kinouchi, Atsuhiro Ichihara, Mariyo Sakoda, Asako Kurauchi-Mito, Kanako Bokuda, Tatsuya Narita, Hideaki Kurosawa, Ge Hong Sun-Wada, Yoh Wada, Taketo Yamada, Minoru Takemoto, Moin A. Saleem, Susan E. Quaggin, Hiroshi Itoh

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Abstract

The prorenin receptor is an accessory subunit of the vacuolar H +-ATPase, suggesting that it has fundamental functions beyond activation of the local renin-angiotensin system. Podocytes express the prorenin receptor, but its function in these cells is unknown. Here, podocyte-specific, conditional, prorenin receptor-knockout mice died of kidney failure and severe proteinuria within 4 weeks of birth. The podocytes of these mice exhibited foot process effacement with reduced and altered localization of the slit-diaphragm proteins nephrin and podocin. Furthermore, the podocytes contained numerous autophagic vacuoles, confirmed by enhanced accumulation of microtubule- associated protein 1 light chain 3-positive intracellular vesicles. Ablation of the prorenin receptor selectively suppressed expression of the V 0 c-subunit of the vacuolar H +-ATPase in podocytes, resulting in deacidification of intracellular vesicles. In conclusion, the prorenin receptor is important for the maintenance of normal podocyte structure and function.

Original languageEnglish
Pages (from-to)2203-2212
Number of pages10
JournalJournal of the American Society of Nephrology
Volume22
Issue number12
DOIs
Publication statusPublished - 2011 Dec 1

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ASJC Scopus subject areas

  • Nephrology

Cite this

Oshima, Y., Kinouchi, K., Ichihara, A., Sakoda, M., Kurauchi-Mito, A., Bokuda, K., Narita, T., Kurosawa, H., Sun-Wada, G. H., Wada, Y., Yamada, T., Takemoto, M., Saleem, M. A., Quaggin, S. E., & Itoh, H. (2011). Prorenin receptor is essential for normal podocyte structure and function. Journal of the American Society of Nephrology, 22(12), 2203-2212. https://doi.org/10.1681/ASN.2011020202