(Pro)renin Receptor Is an Amplifier of Wnt/-Catenin Signaling in Kidney Injury and Fibrosis

Overview

Journal J Am Soc Nephrol

Specialty Nephrology

Date 2017 Mar 9

PMID 28270411

Citations 61

Authors

Zhen Li

Lili Zhou

Yongping Wang

Jinhua Miao

Xue Hong

Fan Fan Hou

Youhua Liu

Affiliations

Soon will be listed here.

Abstract

The (pro)renin receptor (PRR) is a transmembrane protein with multiple functions. However, its regulation and role in the pathogenesis of CKD remain poorly defined. Here, we report that PRR is a downstream target and an essential component of Wnt/-catenin signaling. In mouse models, induction of CKD by ischemia-reperfusion injury (IRI), adriamycin, or angiotensin II infusion upregulated PRR expression in kidney tubular epithelium. Immunohistochemical staining of kidney biopsy specimens also revealed induction of renal PRR in human CKD. Overexpression of either Wnt1 or -catenin induced PRR mRNA and protein expression Notably, forced expression of PRR potentiated Wnt1-mediated -catenin activation and augmented the expression of downstream targets such as fibronectin, plasminogen activator inhibitor 1, and -smooth muscle actin (-SMA). Conversely, knockdown of PRR by siRNA abolished -catenin activation. PRR potentiation of Wnt/-catenin signaling did not require renin, but required vacuolar H ATPase activity. In the mouse model of IRI, transfection with PRR or Wnt1 expression vectors promoted -catenin activation, aggravated kidney dysfunction, and worsened renal inflammation and fibrotic lesions. Coexpression of PRR and Wnt1 had a synergistic effect. In contrast, knockdown of PRR expression ameliorated kidney injury and fibrosis after IRI. These results indicate that PRR is both a downstream target and a crucial element in Wnt signal transmission. We conclude that PRR can promote kidney injury and fibrosis by amplifying Wnt/-catenin signaling.

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