Piezo1 aggravates ischemia/reperfusion-induced acute kidney injury by Ca2+-dependent calpain/HIF-1α/Notch signaling
Macrophages play a vital role in the inflammation and repair processes of ischemia/reperfusion-induced acute kidney injury (IR-AKI). The mechanosensitive ion channel Piezo1 is significant in these inflammatory processes. However, the exact role of macrophage Piezo1 in IR-AKI is unknown. The main pur...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2447801 |
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| author | Xiaoting Chen Jintao Jiang Bin He Shangfei Luo Qiaorui Tan Youfen Yao Rentao Wan Honglin Xu Silin Liu Xianmei Pan Xin Chen Jing Li |
| author_facet | Xiaoting Chen Jintao Jiang Bin He Shangfei Luo Qiaorui Tan Youfen Yao Rentao Wan Honglin Xu Silin Liu Xianmei Pan Xin Chen Jing Li |
| author_sort | Xiaoting Chen |
| collection | DOAJ |
| description | Macrophages play a vital role in the inflammation and repair processes of ischemia/reperfusion-induced acute kidney injury (IR-AKI). The mechanosensitive ion channel Piezo1 is significant in these inflammatory processes. However, the exact role of macrophage Piezo1 in IR-AKI is unknown. The main purpose of this study was to determine the role of macrophage Piezo1 in the injury and repair process in IR-AKI. Genetically modified mice with targeted knockout of Piezo1 in myeloid cells were established, and acute kidney injury was induced by bilateral renal vascular clamping surgery. Additionally, hypoxia treatment was performed on bone marrow-derived macrophages in vitro. Our data indicate that Piezo1 is upregulated in renal macrophages in mice with IR-AKI. Myeloid Piezo1 knockout provided protective effects in mice with IR-AKI. Mechanistically, the regulatory effects of Piezo1 on macrophages are at least partially linked to calpain signaling. Piezo1 activates Ca2+-dependent calpain signaling, which critically upregulates HIF-1α signaling. This key pathway subsequently influences the Notch and CCL2/CCR2 pathways, driving the polarization of M1 macrophages. In conclusion, our findings elucidate the biological functions of Piezo1 in renal macrophages, underscoring its role as a crucial mediator of acute kidney injury. Consequently, the genetic or pharmacological inhibition of Piezo1 presents a promising strategy for treating IR-AKI. |
| format | Article |
| id | doaj-art-6019cc9dcbc2416591dba7b36b48e036 |
| institution | Kabale University |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-6019cc9dcbc2416591dba7b36b48e0362025-01-09T07:02:54ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2024.2447801Piezo1 aggravates ischemia/reperfusion-induced acute kidney injury by Ca2+-dependent calpain/HIF-1α/Notch signalingXiaoting Chen0Jintao Jiang1Bin He2Shangfei Luo3Qiaorui Tan4Youfen Yao5Rentao Wan6Honglin Xu7Silin Liu8Xianmei Pan9Xin Chen10Jing Li11Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaMedical Research Center, Shandong University of Traditional Chinese Medicine, Jinan, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaMacrophages play a vital role in the inflammation and repair processes of ischemia/reperfusion-induced acute kidney injury (IR-AKI). The mechanosensitive ion channel Piezo1 is significant in these inflammatory processes. However, the exact role of macrophage Piezo1 in IR-AKI is unknown. The main purpose of this study was to determine the role of macrophage Piezo1 in the injury and repair process in IR-AKI. Genetically modified mice with targeted knockout of Piezo1 in myeloid cells were established, and acute kidney injury was induced by bilateral renal vascular clamping surgery. Additionally, hypoxia treatment was performed on bone marrow-derived macrophages in vitro. Our data indicate that Piezo1 is upregulated in renal macrophages in mice with IR-AKI. Myeloid Piezo1 knockout provided protective effects in mice with IR-AKI. Mechanistically, the regulatory effects of Piezo1 on macrophages are at least partially linked to calpain signaling. Piezo1 activates Ca2+-dependent calpain signaling, which critically upregulates HIF-1α signaling. This key pathway subsequently influences the Notch and CCL2/CCR2 pathways, driving the polarization of M1 macrophages. In conclusion, our findings elucidate the biological functions of Piezo1 in renal macrophages, underscoring its role as a crucial mediator of acute kidney injury. Consequently, the genetic or pharmacological inhibition of Piezo1 presents a promising strategy for treating IR-AKI.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2447801Piezo1IR-AKImacrophagepolarizationcalpainhypoxia |
| spellingShingle | Xiaoting Chen Jintao Jiang Bin He Shangfei Luo Qiaorui Tan Youfen Yao Rentao Wan Honglin Xu Silin Liu Xianmei Pan Xin Chen Jing Li Piezo1 aggravates ischemia/reperfusion-induced acute kidney injury by Ca2+-dependent calpain/HIF-1α/Notch signaling Renal Failure Piezo1 IR-AKI macrophage polarization calpain hypoxia |
| title | Piezo1 aggravates ischemia/reperfusion-induced acute kidney injury by Ca2+-dependent calpain/HIF-1α/Notch signaling |
| title_full | Piezo1 aggravates ischemia/reperfusion-induced acute kidney injury by Ca2+-dependent calpain/HIF-1α/Notch signaling |
| title_fullStr | Piezo1 aggravates ischemia/reperfusion-induced acute kidney injury by Ca2+-dependent calpain/HIF-1α/Notch signaling |
| title_full_unstemmed | Piezo1 aggravates ischemia/reperfusion-induced acute kidney injury by Ca2+-dependent calpain/HIF-1α/Notch signaling |
| title_short | Piezo1 aggravates ischemia/reperfusion-induced acute kidney injury by Ca2+-dependent calpain/HIF-1α/Notch signaling |
| title_sort | piezo1 aggravates ischemia reperfusion induced acute kidney injury by ca2 dependent calpain hif 1α notch signaling |
| topic | Piezo1 IR-AKI macrophage polarization calpain hypoxia |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2447801 |
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