Peroxiredoxin 5 Acts as a Negative Regulator of the Sodium-Chloride Cotransporter Involved in Alleviating Angiotensin II-Induced Hypertension
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...
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2025-01-01
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| author | Hoon-In Choi In Ae Jung Soo Wan Kim |
| author_facet | Hoon-In Choi In Ae Jung Soo Wan Kim |
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| description | 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. |
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| institution | Kabale University |
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| spelling | doaj-art-1f8cdcddf51b45c4a2ac1296b1e0248f2025-01-24T13:19:29ZengMDPI AGAntioxidants2076-39212025-01-0114110010.3390/antiox14010100Peroxiredoxin 5 Acts as a Negative Regulator of the Sodium-Chloride Cotransporter Involved in Alleviating Angiotensin II-Induced HypertensionHoon-In Choi0In Ae Jung1Soo Wan Kim2Department of Internal Medicine, Chonnam National University Medical School & Hospital, Gwangju 61469, Republic of KoreaDepartment of Internal Medicine, Chonnam National University Medical School & Hospital, Gwangju 61469, Republic of KoreaDepartment of Internal Medicine, Chonnam National University Medical School & Hospital, Gwangju 61469, Republic of KoreaChronic 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.https://www.mdpi.com/2076-3921/14/1/100peroxiredoxin 5 (Prdx5)Angiotensin II (Ang II)sodium-chloride cotransporter (NCC)hypertensionchronic kidney diseases (CKD) |
| spellingShingle | Hoon-In Choi In Ae Jung Soo Wan Kim Peroxiredoxin 5 Acts as a Negative Regulator of the Sodium-Chloride Cotransporter Involved in Alleviating Angiotensin II-Induced Hypertension Antioxidants peroxiredoxin 5 (Prdx5) Angiotensin II (Ang II) sodium-chloride cotransporter (NCC) hypertension chronic kidney diseases (CKD) |
| title | Peroxiredoxin 5 Acts as a Negative Regulator of the Sodium-Chloride Cotransporter Involved in Alleviating Angiotensin II-Induced Hypertension |
| title_full | Peroxiredoxin 5 Acts as a Negative Regulator of the Sodium-Chloride Cotransporter Involved in Alleviating Angiotensin II-Induced Hypertension |
| title_fullStr | Peroxiredoxin 5 Acts as a Negative Regulator of the Sodium-Chloride Cotransporter Involved in Alleviating Angiotensin II-Induced Hypertension |
| title_full_unstemmed | Peroxiredoxin 5 Acts as a Negative Regulator of the Sodium-Chloride Cotransporter Involved in Alleviating Angiotensin II-Induced Hypertension |
| title_short | Peroxiredoxin 5 Acts as a Negative Regulator of the Sodium-Chloride Cotransporter Involved in Alleviating Angiotensin II-Induced Hypertension |
| title_sort | peroxiredoxin 5 acts as a negative regulator of the sodium chloride cotransporter involved in alleviating angiotensin ii induced hypertension |
| topic | peroxiredoxin 5 (Prdx5) Angiotensin II (Ang II) sodium-chloride cotransporter (NCC) hypertension chronic kidney diseases (CKD) |
| url | https://www.mdpi.com/2076-3921/14/1/100 |
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