| Autor: |
Lijie Zeng, Hui Liu, Zhaoyun Liu, Liyan Li, Honglei Wang, Yingying Chen, Junshu Wu, Guanrou Wang, Lijuan Li, Rong Fu |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
SSRN Electronic Journal. |
| ISSN: |
1556-5068 |
| DOI: |
10.2139/ssrn.4202215 |
| Popis: |
Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal disorder of haematopoietic stem cells caused by somatic PIGA mutations, resulting in a deficiency in glycosylphosphatidylinositol-anchored proteins (GPI-AP). Some researchers uncovered that PNH cells displayed a GPI-mediated defect in lipid-raft formation. However, Lipid rafts play a crucial role in signaling, the signaling underlying lipid rafts in PNH have not yet been addressed. In this study, we reported that, IFN-α was significantly increased in PNH plasma compared with normal controls. And PNH cells more resistant to the inhibitory colony[1]-forming activity of IFN-α. Here we have already established PIGA knock out K562 cell line by CRISPR/cas9, the most recognized in vitro model of PNH. PNH cells showed obviously defected endocytosis of IFNα/βRs in lipid rafts, causing suppressed STAT2 activation and the inflammatory response. We further investigated the possible mechanisms of interferon signaling endosomes mediate by cavin1. Our findings provide crucial insight into the process of reduced IFNα signal transduction in PNH cells mediated by lipid rafts and suggest that cavin1 are a potential target for suppression of IFN-α inflammatory signaling. These results might further explain the growth advantage of PNH cells in an unfavorable microenvironment. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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