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作者

Weixing Tan Ning Chen Yang Qiu Xiaomei Feng Shuwen Li Yongjin Zhang Haoran Li Jie Gao Dongbao Zhao

作者单位

Affiliations ¹ Department of Rheumatology and Immunology, Changhai Hospital, The Second Military Medical University, Shanghai, China. ² Air Force Health Care Center for Special Services, Hangzhou, China. ³ Department of Rheumatology and Immunology, The First People's Hospital of Yancheng City, Yancheng, China. ⁴ Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. ⁵ Department of Orthopedics, Changhai Hospital, The Second Military Medical University, Shanghai, China.

刊名

Autoimmunity

年份

2022

卷号

Vol.55 No.5

页码

285-293

ISSN

1607-842X

关键词

Dvl3 RA-FLS ROCK2 RhoA Wnt exosomes inflammation.

摘要

Objective: This study was performed to explore the function and mechanism of Dvl3 in RA-FLS by exosome intervention. Methods: The expression pattern of Dvl3 was examined by IHC, WB, and qPCR. Modified exosomes obtained from culturing supernatant of RA-FLS infected with Dvl3 over expression lentivirus were administrated to the target RA-FLS. The ability of survival, migration, and the production of inflammatory factor influenced by exosomal Dvl3 were detected by CKK8 kits, Tunel, migration test,...更多

Objective: This study was performed to explore the function and mechanism of Dvl3 in RA-FLS by exosome intervention. Methods: The expression pattern of Dvl3 was examined by IHC, WB, and qPCR. Modified exosomes obtained from culturing supernatant of RA-FLS infected with Dvl3 over expression lentivirus were administrated to the target RA-FLS. The ability of survival, migration, and the production of inflammatory factor influenced by exosomal Dvl3 were detected by CKK8 kits, Tunel, migration test, qPCR, and enzyme-linked immunosorbent assay respectively; Flow cytometry analysis was conducted to explorer the inflammatory moderate role of exosomes on CD4+ T cells. The possible downstream pathways of Dvl3 were screened by qPCR and WB and verified by double luciferase reporter experiment. Results: The expression level of Dvl3 was significantly increased in RA and CIA. Exosomes from the OE group could significantly promote cell proliferation activity, migration/invasion ability. The augment of TNF-α, IL-1β, IL-17, and IL-21 was observed in exosomal Dvl3-OE group. Th1 and Th17 cells polarisation and cytokines related were both enhanced by Exosomal Dvl3. Over expression of Dvl3 was accompanied by the significant increase of β-catenin and RhoA activities. Conclusion: This study discovered the high expression of Dvl3 of exosomes derived from RA patients which may possessed the ability to promote phenotypic transformation of RA-FLS through Wnt pathway.收起

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