Gen inhibiting the Wnt/Ca2+ signaling pathway alleviates cerebral ischemia/reperfusion injury
Abstract Cerebral ischemia/reperfusion injury (CIRI) is a major complication of acute ischemic stroke (AIS), characterized by calcium overload, oxidative stress, and cell apoptosis. In this study, we investigated the therapeutic potential of Genistein (Gen) in alleviating CIRI by focusing on its eff...
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| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-88136-8 |
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| author | Li Li Saisai Liu Mengzhe Wang Mengjia Li Yi Liu Haili Chen Jie Chen Weiting Tao Li Huang Shidi Zhao |
| author_facet | Li Li Saisai Liu Mengzhe Wang Mengjia Li Yi Liu Haili Chen Jie Chen Weiting Tao Li Huang Shidi Zhao |
| author_sort | Li Li |
| collection | DOAJ |
| description | Abstract Cerebral ischemia/reperfusion injury (CIRI) is a major complication of acute ischemic stroke (AIS), characterized by calcium overload, oxidative stress, and cell apoptosis. In this study, we investigated the therapeutic potential of Genistein (Gen) in alleviating CIRI by focusing on its effects on the Wnt/Ca2+ signaling pathway. Using a rat model of cerebral ischemia/reperfusion and in vitro experiments on PC12 cells, we observed that Gen treatment reduced infarct size, improved neurological function, and mitigated calcium overload, oxidative stress, and apoptosis. Further analysis revealed that Gen regulates key proteins in the Wnt/Ca2+ signaling pathway, including Wnt5a and Frizzled-2, effectively preventing intracellular calcium accumulation and subsequent damage. The knockdown of Frizzled-2 confirmed the pathway’s role in mediating calcium overload and subsequent damage. Our findings suggest that Gen alleviates CIRI by inhibiting the Wnt/Ca2+ signaling pathway, positioning it as a promising candidate for therapeutic intervention in stroke treatment. |
| format | Article |
| id | doaj-art-b8d38b99a0cb4015af7f4fb9da16c243 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-b8d38b99a0cb4015af7f4fb9da16c2432025-02-09T12:33:36ZengNature PortfolioScientific Reports2045-23222025-02-0115111710.1038/s41598-025-88136-8Gen inhibiting the Wnt/Ca2+ signaling pathway alleviates cerebral ischemia/reperfusion injuryLi Li0Saisai Liu1Mengzhe Wang2Mengjia Li3Yi Liu4Haili Chen5Jie Chen6Weiting Tao7Li Huang8Shidi Zhao9Department of Pathophysiology, Bengbu Medical UniversityDepartment of Pathophysiology, Bengbu Medical UniversityDepartment of Pathophysiology, Bengbu Medical UniversityDepartment of Pathophysiology, Bengbu Medical UniversityClinical Medical School, Bengbu Medical UniversityClinical Medical School, Bengbu Medical UniversityDepartment of Pathophysiology, Bengbu Medical UniversityNanchang Health Vocational CollegeDepartment of Pathophysiology, Bengbu Medical UniversityDepartment of Pathophysiology, Bengbu Medical UniversityAbstract Cerebral ischemia/reperfusion injury (CIRI) is a major complication of acute ischemic stroke (AIS), characterized by calcium overload, oxidative stress, and cell apoptosis. In this study, we investigated the therapeutic potential of Genistein (Gen) in alleviating CIRI by focusing on its effects on the Wnt/Ca2+ signaling pathway. Using a rat model of cerebral ischemia/reperfusion and in vitro experiments on PC12 cells, we observed that Gen treatment reduced infarct size, improved neurological function, and mitigated calcium overload, oxidative stress, and apoptosis. Further analysis revealed that Gen regulates key proteins in the Wnt/Ca2+ signaling pathway, including Wnt5a and Frizzled-2, effectively preventing intracellular calcium accumulation and subsequent damage. The knockdown of Frizzled-2 confirmed the pathway’s role in mediating calcium overload and subsequent damage. Our findings suggest that Gen alleviates CIRI by inhibiting the Wnt/Ca2+ signaling pathway, positioning it as a promising candidate for therapeutic intervention in stroke treatment.https://doi.org/10.1038/s41598-025-88136-8CIRIGenWnt/Ca2+Calcium overload |
| spellingShingle | Li Li Saisai Liu Mengzhe Wang Mengjia Li Yi Liu Haili Chen Jie Chen Weiting Tao Li Huang Shidi Zhao Gen inhibiting the Wnt/Ca2+ signaling pathway alleviates cerebral ischemia/reperfusion injury Scientific Reports CIRI Gen Wnt/Ca2+ Calcium overload |
| title | Gen inhibiting the Wnt/Ca2+ signaling pathway alleviates cerebral ischemia/reperfusion injury |
| title_full | Gen inhibiting the Wnt/Ca2+ signaling pathway alleviates cerebral ischemia/reperfusion injury |
| title_fullStr | Gen inhibiting the Wnt/Ca2+ signaling pathway alleviates cerebral ischemia/reperfusion injury |
| title_full_unstemmed | Gen inhibiting the Wnt/Ca2+ signaling pathway alleviates cerebral ischemia/reperfusion injury |
| title_short | Gen inhibiting the Wnt/Ca2+ signaling pathway alleviates cerebral ischemia/reperfusion injury |
| title_sort | gen inhibiting the wnt ca2 signaling pathway alleviates cerebral ischemia reperfusion injury |
| topic | CIRI Gen Wnt/Ca2+ Calcium overload |
| url | https://doi.org/10.1038/s41598-025-88136-8 |
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