FGF23 promotes renal calcium reabsorption through the TRPV5 channel

被引：198

作者：

Andrukhova, Olena ^{[1
]}

Smorodchenko, Alina ^{[1
]}

Egerbacher, Monika ^{[1
]}

Streicher, Carmen ^{[1
]}

Zeitz, Ute ^{[1
]}

Goetz, Regina ^{[2
]}

Shalhoub, Victoria ^{[3
]}

Mohammadi, Moosa ^{[2
]}

Pohl, Elena E. ^{[1
]}

Lanske, Beate ^{[4
]}

Erben, Reinhold G. ^{[1
]}

机构：

[1] Univ Vet Med Vienna, Vienna, Austria

[2] NYU, Sch Med, New York, NY USA

[3] Amgen Inc, Thousand Oaks, CA 91320 USA

[4] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA

来源：

EMBO JOURNAL | 2014年 / 33卷 / 03期

基金：

奥地利科学基金会;

关键词：

calcium homeostasis; fibroblast growth factor-23; Klotho; renal calcium reabsorption; transient receptor potential vanilloid-5; TRANSCRIPTS ENCODING MEMBRANE; MOUSE KLOTHO GENE; GLUCOSE-HOMEOSTASIS; SODIUM-TRANSPORT; WNK KINASES; MICE; RECEPTOR; EXPRESSION; REGULATOR; FGF-23;

D O I：

10.1002/embj.201284188

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Klotho is thought to activate the epithelial calcium channel Transient Receptor Potential Vanilloid-5 (TRPV5) in distal renal tubules through its putative glucuronidase/sialidase activity, thereby preventing renal calcium loss. However, Klotho also functions as the obligatory co-receptor for fibroblast growth factor-23 (FGF23), a bone-derived phosphaturic hormone. Here, we show that renal calcium reabsorption and renal membrane abundance of TRPV5 are reduced in Fgf23 knockout mice, similar to what is seen in Klotho knockout mice. We further demonstrate that Klotho neither co-localizes with TRPV5 nor is regulated by FGF23. Rather, apical membrane abundance of TRPV5 in renal distal tubules and thus renal calcium reabsorption are regulated by FGF23, which binds the FGF receptor-Klotho complex and activates a signaling cascade involving ERK1/2, SGK1, and WNK4. Our data thereby identify FGF23, not Klotho, as a calcium-conserving hormone in the kidney.

引用

页码：229 / 246

页数：18

共 55 条

[1]

Klotho Prevents Renal Calcium Loss [J].