The expression and implication of TRPV5, Calbindin-D28k and NCX1 in idiopathic hypercalciuria.
The expression of calcium epithelium TRPV5, alcium binding protein Calbindin-D28k and Na(+)/Ca(2+) exchanger NCX1 was detected in renal distal convoluted tubule, and their effects on urine calcium reabsorption and the possible pathogenic mechanism in idiopathic hypercalciuria (IH) were investigated. Genetic hypercalciuric stone-forming (GHS) rats were chosen as animal models to study urine calcium reabsorption and IH. The cognate female and male rats that had maximal urine calcium were matched to breed next generation. Twelve GHS rats and 12 normal control (NC) SD rats were selected. Western blot and real time quantitative PCR were used to detect the protein and gene expression of TRPV5, Calbindin-D28k and NCX1 respectively. The expression levels of TRPV5 protein and mRNA in GHS rats were significantly lower than in NC rats (P<0.05). Western blot revealed that the expression levels of Calbindin-D28k in GHS rats and NC rats were 0.49+/-0.02 and 0.20+/-0.01 respectively, with the difference being significant between them (P<0.05). By using real time quantitative PCR, it was found that there was no significant difference in Calbindin-28k mRNA expression levels between GHS rats and NC rats (P>0.05). There was no significant difference in the NCX1 expression between GHS rats and NC rats (P>0.05). It was suggested that TRPV5 and Calbindin-D28k might play an important role in urine calcium reabsorption and IH, but they differently contributed to the pathogenesis: The down-regulation of TRPV5 decreases urine calcium reabsorption, directly leading to loss of the urine calcium and resulting in hypercalciuria, and the increased Calbindin-D28k expression could relieve, neutralize and decrease intracellular Ca(2+) concentration to maintain calcium balance. NCX1 is not the key protein in urine calcium reabsorption.
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. sgwangtjm@163.com
Shaogang
S
Wang
Dongliang
D
Hu
Qilin
Q
Xi
Shiqiang
S
Su
Jian
J
Bai
Jihong
J
Liu
Zhangqun
Z
Ye
D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D005260:Female; D053565:Hypercalciuria / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D015220:Calcium Channels; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; D019831:Sodium-Calcium Exchanger; D050916:TRPV Cation Channels; C492241:TRPV5 protein, rat; C110374:sodium-calcium exchanger 1