Extracellular HMGB1 Induced Glomerular Endothelial Cell Injury via TLR4/MyD88 Signaling Pathway in Lupus Nephritis
Previously, our study showed that HMGB1 was significantly elevated in the blood and located in the glomerular endothelium in LN patients. But whether extracellular HMGB1 is involved in the injury of glomerular endothelial cells (GECs) in LN still needs further investigation. Firstly, we detected the...
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| Format: | Article |
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Wiley
2021-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/9993971 |
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| author | Tian Yu Feng Xiaojuan Liu Jinxi Miao Xinyan Xu Jie Tian Yuexin Liu Qingjuan Zhang Wei Gu Cunyang Huang Jie Wu Lunbi Zhao Hang Liu Shuxia Guo Huifang |
| author_facet | Tian Yu Feng Xiaojuan Liu Jinxi Miao Xinyan Xu Jie Tian Yuexin Liu Qingjuan Zhang Wei Gu Cunyang Huang Jie Wu Lunbi Zhao Hang Liu Shuxia Guo Huifang |
| author_sort | Tian Yu |
| collection | DOAJ |
| description | Previously, our study showed that HMGB1 was significantly elevated in the blood and located in the glomerular endothelium in LN patients. But whether extracellular HMGB1 is involved in the injury of glomerular endothelial cells (GECs) in LN still needs further investigation. Firstly, we detected the levels of SDC-1, VCAM-1, and proteinuria in LN patients and MRL/lpr mice and analyzed their correlations. Then, HMGB1 and TLR4/MyD88 were inhibited to observe the shedding of glycocalyx and injury of GECs in vivo and in vitro. Our results showed that HRGEC injury and SDC-1 shedding played an important role in the increase of permeability and proteinuria formation in LN. Additionally, inhibition of extracellular HMGB1 and/or downstream TLR4/MyD88/NF-κB/p65 signaling pathway also alleviated GEC monolayer permeability, reduced the shedding of the glomerular endothelial glycocalyx, improved the intercellular tight junction and cytoskeletal arrangement, and downregulated the NO level and VCAM-1 expression. These results suggested that extracellular HMGB1 might involve in GEC injury by activating the TLR4/MyD88 signaling pathway in LN, which provided novel insights and potential therapeutic target for the treatment of lupus nephritis. |
| format | Article |
| id | doaj-art-2e5efda6a3af4f29a8d318c49a0cb8d7 |
| institution | Kabale University |
| issn | 1466-1861 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-2e5efda6a3af4f29a8d318c49a0cb8d72025-02-03T01:20:39ZengWileyMediators of Inflammation1466-18612021-01-01202110.1155/2021/9993971Extracellular HMGB1 Induced Glomerular Endothelial Cell Injury via TLR4/MyD88 Signaling Pathway in Lupus NephritisTian Yu0Feng Xiaojuan1Liu Jinxi2Miao Xinyan3Xu Jie4Tian Yuexin5Liu Qingjuan6Zhang Wei7Gu Cunyang8Huang Jie9Wu Lunbi10Zhao Hang11Liu Shuxia12Guo Huifang13Department of PathologyDepartment of PathologyDepartment of PathologyDepartment of PathologyDepartment of PathologyDepartment of PathologyDepartment of PathologyDepartment of PathologyDepartment of PathologyDepartment of PathologyDepartment of PathologyDepartment of PathologyDepartment of PathologyDepartment of PathologyPreviously, our study showed that HMGB1 was significantly elevated in the blood and located in the glomerular endothelium in LN patients. But whether extracellular HMGB1 is involved in the injury of glomerular endothelial cells (GECs) in LN still needs further investigation. Firstly, we detected the levels of SDC-1, VCAM-1, and proteinuria in LN patients and MRL/lpr mice and analyzed their correlations. Then, HMGB1 and TLR4/MyD88 were inhibited to observe the shedding of glycocalyx and injury of GECs in vivo and in vitro. Our results showed that HRGEC injury and SDC-1 shedding played an important role in the increase of permeability and proteinuria formation in LN. Additionally, inhibition of extracellular HMGB1 and/or downstream TLR4/MyD88/NF-κB/p65 signaling pathway also alleviated GEC monolayer permeability, reduced the shedding of the glomerular endothelial glycocalyx, improved the intercellular tight junction and cytoskeletal arrangement, and downregulated the NO level and VCAM-1 expression. These results suggested that extracellular HMGB1 might involve in GEC injury by activating the TLR4/MyD88 signaling pathway in LN, which provided novel insights and potential therapeutic target for the treatment of lupus nephritis.http://dx.doi.org/10.1155/2021/9993971 |
| spellingShingle | Tian Yu Feng Xiaojuan Liu Jinxi Miao Xinyan Xu Jie Tian Yuexin Liu Qingjuan Zhang Wei Gu Cunyang Huang Jie Wu Lunbi Zhao Hang Liu Shuxia Guo Huifang Extracellular HMGB1 Induced Glomerular Endothelial Cell Injury via TLR4/MyD88 Signaling Pathway in Lupus Nephritis Mediators of Inflammation |
| title | Extracellular HMGB1 Induced Glomerular Endothelial Cell Injury via TLR4/MyD88 Signaling Pathway in Lupus Nephritis |
| title_full | Extracellular HMGB1 Induced Glomerular Endothelial Cell Injury via TLR4/MyD88 Signaling Pathway in Lupus Nephritis |
| title_fullStr | Extracellular HMGB1 Induced Glomerular Endothelial Cell Injury via TLR4/MyD88 Signaling Pathway in Lupus Nephritis |
| title_full_unstemmed | Extracellular HMGB1 Induced Glomerular Endothelial Cell Injury via TLR4/MyD88 Signaling Pathway in Lupus Nephritis |
| title_short | Extracellular HMGB1 Induced Glomerular Endothelial Cell Injury via TLR4/MyD88 Signaling Pathway in Lupus Nephritis |
| title_sort | extracellular hmgb1 induced glomerular endothelial cell injury via tlr4 myd88 signaling pathway in lupus nephritis |
| url | http://dx.doi.org/10.1155/2021/9993971 |
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