Plumbagin rescues the granulosa cell’s pyroptosis by reducing WTAP-mediated N6-methylation in polycystic ovary syndrome
Abstract The survival of ovary granulosa cells (GC) is critical in the initiation and progression of polycystic ovary syndrome (PCOS) in females. Here, we found that the PCOS process is accompanied by massive GC pyroptosis resulting from Caspase-1 inflammasome activation. Administration of plumbagin...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-12-01
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| Series: | Journal of Ovarian Research |
| Online Access: | https://doi.org/10.1186/s13048-022-01058-1 |
| _version_ | 1797965819666235392 |
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| author | Zhaowei Cai Shaojuan He Rongju Liu Liling Zhou Li Zhao |
| author_facet | Zhaowei Cai Shaojuan He Rongju Liu Liling Zhou Li Zhao |
| author_sort | Zhaowei Cai |
| collection | DOAJ |
| description | Abstract The survival of ovary granulosa cells (GC) is critical in the initiation and progression of polycystic ovary syndrome (PCOS) in females. Here, we found that the PCOS process is accompanied by massive GC pyroptosis resulting from Caspase-1 inflammasome activation. Administration of plumbagin, an effective compound isolated from plant medicine, can prevent the pyroptosis of GC and the onset of PCOS. Mechanistic study indicates the over-activation of the inflammasome in GC is due to the upregulation of WTAP, a key regulator of the RNA N6-methylase complex. WTAP mediates the mRNA N6-methylation of NLRP3 inflammasome component ASC and enhances ASC RNA stability, which results in the overactivation of the inflammasome in GCs from the PCOS model. Plumbagin treatment suppresses the WTAP-mediated N6-methylation of ASC mRNA and reduces the pyroptosis of GCs. This study supports the profound potential of plumbagin in PCOS treatment. Graphical Abstract |
| first_indexed | 2024-04-11T02:06:05Z |
| format | Article |
| id | doaj.art-3887a96c793b4f32b9bf2ecb4d5920bf |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-11T02:06:05Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-3887a96c793b4f32b9bf2ecb4d5920bf2023-01-03T03:06:12ZengBMCJournal of Ovarian Research1757-22152022-12-0115111510.1186/s13048-022-01058-1Plumbagin rescues the granulosa cell’s pyroptosis by reducing WTAP-mediated N6-methylation in polycystic ovary syndromeZhaowei Cai0Shaojuan He1Rongju Liu2Liling Zhou3Li Zhao4Reproductive Center, SSL central hospital of DongguanDepartment of clinical laboratory affiliated Dongguan hospital (Dongguan People’s Hospital), Southern Medical UniversityReproductive Center, SSL central hospital of DongguanReproductive Center, SSL central hospital of DongguanReproductive Center, SSL central hospital of DongguanAbstract The survival of ovary granulosa cells (GC) is critical in the initiation and progression of polycystic ovary syndrome (PCOS) in females. Here, we found that the PCOS process is accompanied by massive GC pyroptosis resulting from Caspase-1 inflammasome activation. Administration of plumbagin, an effective compound isolated from plant medicine, can prevent the pyroptosis of GC and the onset of PCOS. Mechanistic study indicates the over-activation of the inflammasome in GC is due to the upregulation of WTAP, a key regulator of the RNA N6-methylase complex. WTAP mediates the mRNA N6-methylation of NLRP3 inflammasome component ASC and enhances ASC RNA stability, which results in the overactivation of the inflammasome in GCs from the PCOS model. Plumbagin treatment suppresses the WTAP-mediated N6-methylation of ASC mRNA and reduces the pyroptosis of GCs. This study supports the profound potential of plumbagin in PCOS treatment. Graphical Abstracthttps://doi.org/10.1186/s13048-022-01058-1 |
| spellingShingle | Zhaowei Cai Shaojuan He Rongju Liu Liling Zhou Li Zhao Plumbagin rescues the granulosa cell’s pyroptosis by reducing WTAP-mediated N6-methylation in polycystic ovary syndrome Journal of Ovarian Research |
| title | Plumbagin rescues the granulosa cell’s pyroptosis by reducing WTAP-mediated N6-methylation in polycystic ovary syndrome |
| title_full | Plumbagin rescues the granulosa cell’s pyroptosis by reducing WTAP-mediated N6-methylation in polycystic ovary syndrome |
| title_fullStr | Plumbagin rescues the granulosa cell’s pyroptosis by reducing WTAP-mediated N6-methylation in polycystic ovary syndrome |
| title_full_unstemmed | Plumbagin rescues the granulosa cell’s pyroptosis by reducing WTAP-mediated N6-methylation in polycystic ovary syndrome |
| title_short | Plumbagin rescues the granulosa cell’s pyroptosis by reducing WTAP-mediated N6-methylation in polycystic ovary syndrome |
| title_sort | plumbagin rescues the granulosa cell s pyroptosis by reducing wtap mediated n6 methylation in polycystic ovary syndrome |
| url | https://doi.org/10.1186/s13048-022-01058-1 |
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