Objective
To explore the role of protein arginine methyltransferase 1 (PRMT1) in the development of rheumatoid arthritis (RA).
Methods
Fibroblast‐like synoviocytes (FLS) were isolated from synovial tissues, cultured and transfected with plasmid vector or short hairpin RNA (shRNA). The morphology and surface markers of FLS were investigated by light microscopy and flow cytometry. The expression levels of PRMT1, Zeste Homolog 2 (EZH2), matrix metalloproteinase‐2 (MMP‐2) and MMP‐9 were detected by real‐time polymerase chain reaction and Western blotting. Cell viability was tested by MTT assay, cell proliferation was assessed by EdU assay, cell invasion was evaluated by Transwell invasion test, cell migration was detected by wound healing assay, and cell apoptosis was detected by flow cytometry.
Results
The expression of PRMT1 was elevated in RA synovial tissues compared with control tissues. FLS from control tissues showed a lower level of PRMT1 than FLS from RA tissues, and FLS from RA tissues had a stronger ability of cell survival and metastasis than those from control tissues. When silencing PRMT1 expression, FLS from RA tissues showed a decreased ability of cell survival and metastasis. Additionally, FLS from RA tissues expressed a higher level of MMP‐2 and MMP‐9. When silencing PRMT1 expression, the expression of MMP‐2 and MMP‐9 of FLS was suppressed. Furthermore, the effect of PRMT1 on FLS was mediated by EZH2.
Conclusion
We found that PRMT1 had an overall effect on FLS via EZH2, which contributed to the development of RA. Hence, PRMT1 and EZH2 provide potential targets for RA treatment.
Aim: Midkine inhibition ameliorates sepsis induced lung injury. This research was to explore the influences of midkine on the sepsis-associated heart damage and the mechanisms.
Methods: Sepsis models were established via lipopolysaccharide (LPS) induction in mice in vivo, and in HL-1 cells in vitro.
Results: The expressed levels of midkine raised in the heart of mice and HL-1 cells by treating with LPS. The cardiac dysfunction of septic mice was deteriorated by midkine overexpression and was improved by midkine knockdown. The increases of inflammatory factors in the heart of mice induced by LPS were further enhanced by midkine overexpression and were attenuated by midkine knockdown. The increase of myocardial apoptosis in septic mice was worsened after midkine overexpression and was alleviated after midkine downregulation. The oxidative stress increase in the heart of septic mice was exacerbated by overexpression of midkine and was attenuated by downregulation of midkine.
Conclusions: These results indicated that midkine exacerbated cardiac dysfunction via enhanced inflammation, apoptosis and oxidative stress. Targeting of midkine could improve cardiac dysfunction via attenuation of inflammation, apoptosis and oxidative stress.
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