Protective Roles of Xenotropic and Polytropic Retrovirus Receptor 1 (XPR1) in Uremic Vascular Calcification

Hokuto Arase, Shunsuke Yamada, Kumiko Torisu, Masanori Tokumoto, Masatomo Taniguchi, Kazuhiko Tsuruya, Toshiaki Nakano, Takanari Kitazono

研究成果: ジャーナルへの寄稿学術誌査読

2 被引用数 (Scopus)


Cellular phosphate transporters play critical roles in the pathogenesis of vascular calcification (VC) in chronic kidney disease (CKD). However, the mechanistic link between VC and xenotropic and polytropic receptor 1 (XPR1), a newly identified phosphate exporter, remains unknown. We developed a new mouse model with rapidly progressive uremic VC in C57BL/6 mice and examined the roles of XPR1. The combination of surgical heminephrectomy and 8 weeks of feeding a customized warfarin and adenine-based diet induced extensive aortic VC in almost all mice. The XPR1 mRNA level in the aorta of CKD mice was significantly lower than those in control mice as early as week 2, when there was no apparent VC, which progressively declined thereafter. Dietary phosphate restriction increased XPR1 mRNA expression in the aorta but reduced aortic VC in CKD mice. In cultured vascular smooth muscle cells (VSMCs), a calcifying medium supplemented with high phosphate and calcium did not affect XPR1 mRNA expression. The XPR1 mRNA expression in cultured VCMCs was also unaffected by administration of indoxyl sulfate or calcitriol deficiency but was decreased by 1–34 parathyroid hormone or fibroblast growth factor 23 supplementation. Furthermore, XPR1 deletion in the cultured VSMCs exacerbated calcification of the extracellular matrix as well as the osteogenic phenotypic switch under the condition of calcifying medium. Our data suggest that XPR1 plays protective roles in the pathogenesis of VC and its decrease in the aorta may contribute to the progression of VC in CKD.

ジャーナルCalcified Tissue International
出版ステータス出版済み - 6月 2022

!!!All Science Journal Classification (ASJC) codes

  • 内分泌学、糖尿病および代謝内科学
  • 整形外科およびスポーツ医学
  • 内分泌学


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