The expression and implication of TRPV5, Calbindin-D28k and NCX1 in idiopathic hypercalciuria
Shaogang Wang1, Dongliang Hu, Qilin Xi
1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. sgwangtjm@163.com
Abstract:
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.
Insights
Reduced TRPV5 expression in genetic hypercalciuric stone-forming rats leads to lower urine calcium reabsorption and idiopathic hypercalciuria. Increased Calbindin-D28k expression may help maintain calcium balance.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- Idiopathic hypercalciuria (IH) is a condition characterized by excessive calcium in the urine.
- Understanding the molecular mechanisms of IH is crucial for developing effective treatments.
- Renal calcium handling proteins, including TRPV5, Calbindin-D28k, and NCX1, play key roles in calcium reabsorption.
Purpose of the Study:
- To investigate the expression of TRPV5, Calbindin-D28k, and NCX1 in the renal distal convoluted tubule of genetic hypercalciuric stone-forming (GHS) rats.
- To elucidate the role of these proteins in urine calcium reabsorption and the pathogenesis of IH.
- To identify potential therapeutic targets for managing IH.
Main Methods:
- Utilized genetic hypercalciuric stone-forming (GHS) rats as an animal model for IH.
- Employed Western blot to detect protein expression levels of TRPV5, Calbindin-D28k, and NCX1.
- Applied real-time quantitative PCR to assess the gene expression of TRPV5, Calbindin-D28k, and NCX1.
Main Results:
- Significantly lower expression of TRPV5 protein and mRNA was observed in GHS rats compared to normal control (NC) rats.
- Calbindin-D28k protein expression was significantly higher in GHS rats than in NC rats, while mRNA levels showed no significant difference.
- No significant differences in NCX1 expression were found between GHS and NC rats.
Conclusions:
- Down-regulation of TRPV5 directly reduces urine calcium reabsorption, leading to hypercalciuria in IH.
- Increased Calbindin-D28k protein expression may serve a compensatory role in maintaining intracellular calcium balance.
- TRPV5 and Calbindin-D28k are implicated in IH pathogenesis, with TRPV5 playing a direct role in calcium loss, while NCX1 is not a key factor.
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