Effect and mechanism of Dickkopf-related protein 1 on urinary sodium excretion in spontaneously hypertensive rats

Fangling CHENG; Hongyong WANG; Yongjian YANG

doi:10.16016/j.1000-5404.202005002

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Effect and mechanism of Dickkopf-related protein 1 on urinary sodium excretion in spontaneously hypertensive rats

更新时间：2026-01-09

- Effect and mechanism of Dickkopf-related protein 1 on urinary sodium excretion in spontaneously hypertensive rats
- Journal of Third Military Medical University Vol. 42, Issue 19, Pages: 1920-1929(2020)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the Key Program of Natural Science Foundation of Chongqing(CSTC2015jcyjBX0129)
- DOI：10.16016/j.1000-5404.202005002
  CLC：
- Received：01 May 2020，
  
  Published：15 October 2020
- 稿件说明：
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Fangling CHENG, Hongyong WANG, Yongjian YANG. Effect and mechanism of Dickkopf-related protein 1 on urinary sodium excretion in spontaneously hypertensive rats[J]. Journal of Third Military Medical University, 2020, 42(19): 1920-1929.
DOI：

Fangling CHENG, Hongyong WANG, Yongjian YANG. Effect and mechanism of Dickkopf-related protein 1 on urinary sodium excretion in spontaneously hypertensive rats[J]. Journal of Third Military Medical University, 2020, 42(19): 1920-1929. DOI： 10.16016/j.1000-5404.202005002.

摘要

Abstract

Objective

To explore the role of Dickkopf-related protein 1 (DKK1) in hypertension and its effect on urinary sodium excretion.

Methods

Twelve rats with normal blood pressure (Wister Kyoto rats

WKY)

and 12 primary hypertension rats (spontaneously hypertensive rats

SHRs)

all male

at an age of 8~10 weeks

weighing 190~210 g

were employed in this study. The expression of DKK1 and β-catenin in the kidney of WKY and SHR rats was detected by West

ern blotting. Then 12 WKY rats were randomly divided into WKY+DKK1 group and WKY control group (

=6)

and so were the 12 SHR rats. Recombinant protein DKK 16 ng/(g·d) was pumped into the rats from the DKK1 groups

via

micro-syringe. The blood pressure of all the rats was measured by non-invasive tail-cuff method. And the urine was collected by metabolic cages for 24-hour urinary volume and urinary sodium

which were adjusted with their weight. The expression of DKK1 and β-catenin protein in renal proximal tubule epithelial (RPT) cells (WKY-RPT and SHR-RPT) was detected by Western blotting. After intervention with recombinant protein DKK1

DKK1 siRNA (siDKK1)

and β-catenin nuclear signal inhibitor (inhibitor of β-catenin-responsive transcription

ICRT 14)

inhibitor of GSK3β (6-bromoindirubin-3′-oxime

BIO)

the expression of DKK1 and β-catenin and the activity of Na

-K

-ATPase were measured.

Results

The expression level of DKK1 was lower

while that of β-catenin (indicating Wnt/β-catenin was activated) was higher in the renal tissue of SHR rats than of WKY rats. When the SHR+ DKK1 group was compared with the SHR group

the systolic blood pressure was significantly decreased at 2 weeks after implantation (145.21±2.83

156.07±3.08 mmHg

0.05)

and both urine volume (37.40±3.76

27.24±2.30 mL/kg

0.05) and urinary sodium excretion (0.79±0.09

0.51±0.09 mmol/kg

0.05) within 24 h were increased. There were no significant differences in above indexes between WKY+DKK1 group and WKY group. The expression of DKK1 was lower in the SHR-RPT cells than the WKY-RPT cells

and that of β-catenin was opposite. Intervention of DKK1 expression would cause the change of β-catenin (indicating the alteration of Wnt/β-catenin pathway)

and thus affect the activity of Na

-K

-ATPase

and the activity of

-K

-ATPase was negatively correlated with DKK1.

Conclusion

DKK1 can reduce Na

-K

-ATPase activity at least partially by inhibiting the Wnt/β-catenin pathway

promote urinary sodium excretion and lower blood pressure.

关键词

Keywords

references

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