Inhibitory effect of curcumol on Jak2-STAT signal pathway molecules of fibroblast-like synoviocytes

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  Purpose: Synovial membrane hyperplasia of rheumatoid arthritis (RA) is a critical pathological foundation for inducing articular injury.The janus kinase and Signal Transducer and Activator of Transcription (Jak-STAT) pathway plays a critical role in synovial membrane proliferation induced by platelet-derived growth factor (PDGF).To explore the anti-cell proliferation mechanism of curcumol, a pure monomer extracted from Chinese medical plant zedoary rhizome, the changes of Jak2-STAT1/3 signal pathway related molecules in synoviocytes were observed in vitro.Methods: In the study, the fibroblast-like synoviocytes (FLS) in patients with RA were collected and cultured.The following parameters were measured: cell proliferation (WST-1 assay), cell cycles (fluorescence-activated cell sorting, FACS), the mRNA expression of STAT1, STAT3, SOCS1 and SOCS3 (fluorescent quantitative-polymerase chain reaction, FQ-PCR), STAT1 and STAT3 activities (electrophoretic mobility shift assay, EMSA), the protein expressions of phosphorylated Jak2,STAT1 and STAT3 (Western Blotting).Results: It was shown that certain concentration curcumol including 25 g/ml, 50 g/ml and 100 g/ml could inhibit the RA synoviocyte proliferation and DNA synthesis induced by PDGF-BB though it had no effect on the mRNA expression of STAT1, STAT3, SOCS1 and SOCS3 in vitro.The transcription factors activities and protien expression of STAT1 and STAT3 were obviously elevated after PDGF-BB stimulation, meanwhile, the different concentraion curcumol could down-regulated the DNA binding activities of STAT1 and STAT3.The curcumol at the concentration of 100 g/ml could inhibit the phosphorylation of JAK2 and the expression of STAT1 protein while it had no effect on the protein expressions of STAT3, SOCS 1 and SOCS3.Conclusion: The curcumol might suppress the FLS proliferation and DNA synthesis induced by PDGF-BB through attenuating Jak2 phosphorylation, down-regulating STAT1 and STAT3 DNA binding activities, which provide theoretical foundation for clinical RA treatment of curcumol.
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