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过氧化物酶体增殖物激活受体5作为氯化钠共转运体的负调节因子，参与减轻血管紧张素II诱导的高血压。

Peroxiredoxin 5 Acts as a Negative Regulator of the Sodium-Chloride Cotransporter Involved in Alleviating Angiotensin II-Induced Hypertension.

作者信息

Choi Hoon-In, Jung In Ae, Kim Soo Wan

机构信息

Department of Internal Medicine, Chonnam National University Medical School & Hospital, Gwangju 61469, Republic of Korea.

出版信息

Antioxidants (Basel). 2025 Jan 16;14(1):100. doi: 10.3390/antiox14010100.

DOI:10.3390/antiox14010100
PMID:39857434
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11761572/
Abstract

Chronic kidney disease (CKD) and hypertension are interconnected, worsening each other. Recent studies have shown that the reduction of peroxiredoxin 5 (Prdx5) accelerates kidney fibrosis, a hallmark of CKD. This study aims to observe whether the deficiency of Prdx5 also contributes to the worsening of CKD-related hypertension. Angiotensin II (Ang II, 1000 ng/kg/day) was infused into Prdx5 wild-type (WT) and Prdx5 knock out (KO) mice (each group; n = 6). The blood pressure was higher in the Ang-II-infused Prdx5 KO mice than in the WT mice. Ang-II-induced ROS/RNS generation and fibrotic marker expressions were also higher in the Prdx5 KO mice. In particular, the expression of the sodium-chloride cotransporter (NCC), an ion transport protein important for sodium retention in the distal convoluted tubule, and the NCC's phosphorylation at Thr53 were increased in the kidney of Ang-II-infused Prdx5 KO. The activity of an WNK4-SPAK/OSR1, upstream activator of the NCC, was also increased. In 209/mDCT cells, the knockdown of Prdx5 (siPrdx5) increased the activity of Ang-II-mediated WNK4-SPAK/OSR1-NCC signaling and Ang-II-mediated ROS generation, whereas Prdx5 overexpression showed opposite results. In conclusion, Prdx5 negatively regulates the WNK4-SPAK/OSR1-NCC signaling axis, indicating its potential as a candidate for antihypertensive drug development through NCC regulation.

摘要

慢性肾脏病（CKD）与高血压相互关联，相互恶化。最近的研究表明，过氧化物还原酶5（Prdx5）的减少会加速肾纤维化，这是CKD的一个标志。本研究旨在观察Prdx5的缺乏是否也会导致CKD相关高血压的恶化。将血管紧张素II（Ang II，1000 ng/kg/天）注入Prdx5野生型（WT）和Prdx5基因敲除（KO）小鼠（每组n = 6）。注入Ang-II的Prdx5 KO小鼠的血压高于WT小鼠。Ang-II诱导的活性氧/氮化物（ROS/RNS）生成和纤维化标志物表达在Prdx5 KO小鼠中也更高。特别是，在注入Ang-II的Prdx5 KO小鼠的肾脏中，对远端曲小管中钠潴留很重要的离子转运蛋白氯化钠共转运体（NCC）的表达以及NCC在苏氨酸53处的磷酸化增加。NCC的上游激活剂WNK4-SPAK/OSR1的活性也增加。在209/mDCT细胞中，敲低Prdx5（siPrdx5）增加了Ang-II介导的WNK4-SPAK/OSR1-NCC信号传导活性和Ang-II介导的ROS生成，而Prdx5过表达则显示出相反的结果。总之，Prdx5负向调节WNK4-SPAK/OSR1-NCC信号轴，表明其作为通过调节NCC开发抗高血压药物候选物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/536bbf24f698/antioxidants-14-00100-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/054be105444c/antioxidants-14-00100-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/f21405c5d67b/antioxidants-14-00100-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/46095042058d/antioxidants-14-00100-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/ca463c724164/antioxidants-14-00100-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/cdb42d5418b5/antioxidants-14-00100-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/b3b21d75619c/antioxidants-14-00100-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/840ed06f7785/antioxidants-14-00100-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/ff1a3f22e368/antioxidants-14-00100-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/536bbf24f698/antioxidants-14-00100-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/054be105444c/antioxidants-14-00100-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/f21405c5d67b/antioxidants-14-00100-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/46095042058d/antioxidants-14-00100-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/ca463c724164/antioxidants-14-00100-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/cdb42d5418b5/antioxidants-14-00100-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/b3b21d75619c/antioxidants-14-00100-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/840ed06f7785/antioxidants-14-00100-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/ff1a3f22e368/antioxidants-14-00100-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/11761572/536bbf24f698/antioxidants-14-00100-g009.jpg

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