Abstract | INTRODUCTION: Previous studies have confirmed the pathologic role of synovial aquaporin 1 (AQP1) in rheumatoid arthritis (RA), but its associations with the abnormal biologic behaviors of fibroblast-like synoviocytes (FLS) remain unclear. Herein, we examined the roles of AQP1 in the proliferation, migration and invasion of TNF-α-stimulated RA FLS (MH7A cells) and explored the underlying mechanisms. MATERIALS AND METHODS: Lentivirus-mediated AQP1 overexpression or silencing MH7A cells was constructed. Assays of MTT, flow cytometry (PI staining and Annexin V-PE/7-AAD staining), TMRM staining, wound-healing, transwell and phalloidin staining were performed to detect cell proliferation, cycle distribution, apoptosis, migration and invasion. The involvement of Wnt/β- catenin pathway was revealed by Western blot and β- catenin immunofluorescence staining. RESULTS: AQP1 overexpression promoted cell proliferation of TNF-α-stimulated MH7A by facilitating transformation from G0/G1 to S phase and inhibiting cell apoptosis (ie, reduced apoptosis rates, raised mitochondrial membrane potential, increased Bcl-2 protein level and decreased levels of Bax and cleaved caspase 3 protein). Also, AQP1 overexpression increased the migration index as well as the numbers of migrated and invasive cells. Furthermore, AQP1 overexpression promoted the activation of Wnt/β- catenin pathway, and XAV939, an inhibitor of Wnt/β- catenin, canceled the above effects of AQP1 overexpression on MH7A cells. As expected, AQP1 silencing exhibited the opposite effects on TNF-α-stimulated MH7A cells, which could be reversed by LiCl, an activator of Wnt/β- catenin. CONCLUSION: AQP1 can affect the proliferation, migration and invasion of MH7A cells by Wnt/β- catenin signaling pathway, and AQP1 can be as a crucial determiner that can regulate RA FLS biologic behaviors.
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Authors | Meng-Yuan Zhou, Li Cai, Xiao-Wen Feng, Yu-Rong Mu, Bo Meng, Fang-Yuan Liu, Rong Li |
Journal | Journal of inflammation research
(J Inflamm Res)
Vol. 14
Pg. 1945-1957
( 2021)
ISSN: 1178-7031 [Print] New Zealand |
PMID | 34017191
(Publication Type: Journal Article)
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Copyright | © 2021 Zhou et al. |