Activation of Piezo1 downregulates renin in juxtaglomerular cells and contributes to blood pressure homeostasis
Abstract Background The synthesis and secretion of renin in juxtaglomerular (JG) cells are closely regulated by the blood pressure. To date, however, the molecular identity through which JG cells respond to the blood pressure remains unclear. Results Here we discovered that Piezo1, a mechanosensitiv...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-022-00931-2 |
| _version_ | 1811203681394098176 |
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| author | Xiaoqiang Yang Honghui Zeng Le Wang Siweier Luo Yiming Zhou |
| author_facet | Xiaoqiang Yang Honghui Zeng Le Wang Siweier Luo Yiming Zhou |
| author_sort | Xiaoqiang Yang |
| collection | DOAJ |
| description | Abstract Background The synthesis and secretion of renin in juxtaglomerular (JG) cells are closely regulated by the blood pressure. To date, however, the molecular identity through which JG cells respond to the blood pressure remains unclear. Results Here we discovered that Piezo1, a mechanosensitive ion channel, was colocalized with renin in mouse kidney as well as As4.1 cells, a commonly used JG cell line. Activation of Piezo1 by its agonist Yoda1 induced an intracellular calcium increase and downregulated the expression of renin in these cells, while knockout of Piezo1 in JG cells abolished the effect of Yoda1. Meanwhile, mechanical stress using microfluidics also induced an intracellular calcium increase in wildtype but not Piezo1 knockout JG cells. Mechanistically, we demonstrated that activation of Piezo1 upregulated the Ptgs2 expression via the calcineurin-NFAT pathway and increased the production of Ptgs2 downstream molecule PGE2 in JG cells. Surprisingly, we discovered that increased PGE2 could decreased the renin expression through the PGE2 receptor EP1 and EP3, which inhibited the cAMP production in JG cells. In mice, we found that activation of Piezo1 significantly downregulated the renin expression and blood pressure in wildtype but not adeno-associated virus (AAV)-mediated kidney specific Piezo1 knockdown mice. Conclusions In summary, these results revealed that activation of Piezo1 could downregulate the renin expression in JG cells and mice, subsequently a reduction of blood pressure, highlighting its therapeutic potential as a drug target of the renin-angiotensin system. |
| first_indexed | 2024-04-12T02:59:43Z |
| format | Article |
| id | doaj.art-a23be08134ac4d40957ba7d8d9e314e3 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-04-12T02:59:43Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-a23be08134ac4d40957ba7d8d9e314e32022-12-22T03:50:42ZengBMCCell & Bioscience2045-37012022-12-0112111710.1186/s13578-022-00931-2Activation of Piezo1 downregulates renin in juxtaglomerular cells and contributes to blood pressure homeostasisXiaoqiang Yang0Honghui Zeng1Le Wang2Siweier Luo3Yiming Zhou4Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityAbstract Background The synthesis and secretion of renin in juxtaglomerular (JG) cells are closely regulated by the blood pressure. To date, however, the molecular identity through which JG cells respond to the blood pressure remains unclear. Results Here we discovered that Piezo1, a mechanosensitive ion channel, was colocalized with renin in mouse kidney as well as As4.1 cells, a commonly used JG cell line. Activation of Piezo1 by its agonist Yoda1 induced an intracellular calcium increase and downregulated the expression of renin in these cells, while knockout of Piezo1 in JG cells abolished the effect of Yoda1. Meanwhile, mechanical stress using microfluidics also induced an intracellular calcium increase in wildtype but not Piezo1 knockout JG cells. Mechanistically, we demonstrated that activation of Piezo1 upregulated the Ptgs2 expression via the calcineurin-NFAT pathway and increased the production of Ptgs2 downstream molecule PGE2 in JG cells. Surprisingly, we discovered that increased PGE2 could decreased the renin expression through the PGE2 receptor EP1 and EP3, which inhibited the cAMP production in JG cells. In mice, we found that activation of Piezo1 significantly downregulated the renin expression and blood pressure in wildtype but not adeno-associated virus (AAV)-mediated kidney specific Piezo1 knockdown mice. Conclusions In summary, these results revealed that activation of Piezo1 could downregulate the renin expression in JG cells and mice, subsequently a reduction of blood pressure, highlighting its therapeutic potential as a drug target of the renin-angiotensin system.https://doi.org/10.1186/s13578-022-00931-2Piezo1 ion channelReninCalcium signalingJuxtaglomerular cellMechanical stressBlood pressure homeostasis |
| spellingShingle | Xiaoqiang Yang Honghui Zeng Le Wang Siweier Luo Yiming Zhou Activation of Piezo1 downregulates renin in juxtaglomerular cells and contributes to blood pressure homeostasis Cell & Bioscience Piezo1 ion channel Renin Calcium signaling Juxtaglomerular cell Mechanical stress Blood pressure homeostasis |
| title | Activation of Piezo1 downregulates renin in juxtaglomerular cells and contributes to blood pressure homeostasis |
| title_full | Activation of Piezo1 downregulates renin in juxtaglomerular cells and contributes to blood pressure homeostasis |
| title_fullStr | Activation of Piezo1 downregulates renin in juxtaglomerular cells and contributes to blood pressure homeostasis |
| title_full_unstemmed | Activation of Piezo1 downregulates renin in juxtaglomerular cells and contributes to blood pressure homeostasis |
| title_short | Activation of Piezo1 downregulates renin in juxtaglomerular cells and contributes to blood pressure homeostasis |
| title_sort | activation of piezo1 downregulates renin in juxtaglomerular cells and contributes to blood pressure homeostasis |
| topic | Piezo1 ion channel Renin Calcium signaling Juxtaglomerular cell Mechanical stress Blood pressure homeostasis |
| url | https://doi.org/10.1186/s13578-022-00931-2 |
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