Calcineurin Aβ is central to the expression of the renal type IINa/Pi co-transporter gene and to the regulation of renal phosphate transport

被引:23
作者
Moz, Y
Levi, R
Lavi-Moshayoff, V
Cox, KB
Molkentin, JD
Silver, J
Naveh-Many, T
机构
[1] Hadassah Hebrew Univ, Med Ctr, Minerva Ctr Calcium & Bone Metab, Nephrol & Hypertens Serv, Jerusalem, Israel
[2] Univ Cincinnati, Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2004年 / 15卷 / 12期
关键词
D O I
10.1097/01.ASN.0000144207.44469.BE
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
The sensing and response to extracellular phosphate (Pi) concentration is preserved from prokaryotes to mammals and ensures an adequate supply of Pi in the face of large differences in its availability. In mammals, the kidneys are central to Pi homeostasis. Renal Pi reabsorption is mediated by a Na/Pi co-transporter that is regulated by a renal Pi sensing system and Immoral factors. The signal transduction by which Pi regulates type 11 Na/Pi activity is largely unknown. It is shown that calcineurin inhibitors specifically and dramatically decrease type 11 Na/Pi gene expression in a proximal tubule cell line and in vivo. Mice with genetic deletion of the calcineurin Abeta gene had a marked decrease in type II Na/Pi mRNA levels and remarkably did not show the expected increase in type 11 Na/Pi mRNA levels after the challenge of a low-Pi diet. In contrast, the regulation of renal 25(OH)-vitamin D 1 a-hydroxylase gene expression by Pi was intact. This is the first demonstration that calcineurin has a crucial role in the signal transduction pathway regulating renal Pi homeostasis both in vitro and in vivo. These results suggest that the use of calcineurin inhibitors contributes to the renal Pi wasting seen in renal transplant patients.
引用
收藏
页码:2972 / 2980
页数:9
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