Prorenin Receptor Is Essential for Normal Podocyte Structure and Function

Y Oshima, K Kinouchi, A Ichihara, M Sakoda, A Kurauchi-Mito, K Bokuda, T Narita, H Kurosawa, GH Sun-Wada, Y Wada, T Yamada, M Takemoto, MA Saleem, SE Quaggin, H Itoh

Research output: Contribution to journalArticle (Academic Journal)peer-review

132 Citations (Scopus)

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.
Translated title of the contributionProrenin Receptor Is Essential for Normal Podocyte Structure and Function
Original languageEnglish
JournalJournal of the American Society of Nephrology
Publication statusPublished - Nov 2011

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