| Autor: |
Shanshan Yu, Ying Lu, Ming Zong, Qi Tan, Lieying Fan |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Arthritis Research & Therapy, Vol 21, Iss 1, Pp 1-10 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
1478-6362 |
| DOI: |
10.1186/s13075-019-1861-7 |
| Popis: |
Abstract Background Hypoxia plays an important role in the proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), leading to pathology of RA. This study was conducted to evaluate hypoxia-induced microRNAs (hypoxamiR) in RA-FLS and its role in the function of RA-FLS. Methods RA-FLS were cultured under normoxia (21% O2) or hypoxia (3% O2) condition, followed by a microRNA (miRNA) array analysis. The upregulation of miR-191 by hypoxia was confirmed in RA-FLS and FLS from osteoarthritis (OA) patients by quantitative real-time polymerase chain reaction (RT-PCR). Transfection of miR-191 mimic and inhibitor was used to investigate the function of miR-191 in RA-FLS. The functional targets of miR-191 were predicted by bioinfomatics and then validated by reporter gene assay. Results A subset of miRNAs was identified to be induced by hypoxia including miR-191. The upregulation of miR-191 was found to be specific in hypoxic RA-FLS, compared to hypoxic OA-FLS. We observed that miR-191 in RA-FLS increased cellular proliferation via promoting G1/S transition of the cell cycle and suppressed cell apoptosis induced by cell starvation. Bioinformatical analysis and experimental assays identified CCAAT/enhancer binding protein β (C/EBPβ) as a target gene of miR-191 in RA-FLS. Enforced expression of C/EBPβ rescued the cellular phenotypes induced by miR-191. In addition, an inverse correlation between the C/EBPβ level and hypoxia stimulation was found in RA-FLS, and overexpression of C/EBPβ could partly rescue the hypoxia-induced cell proliferation. Conclusion We demonstrated the miR-191-C/EBPβ signaling pathway mediating the hypoxia-induced cell proliferation in RA. |
| Databáze: |
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| Externí odkaz: |
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