木犀草素通过酪氨酸激酶2/信号转导及转录激活因子3信号通路对增生性瘢痕成纤维细胞增殖、凋亡和迁移的影响OA

Objective To investigate whether luteolin modulates proliferation,apoptosis,and migration of human hypertrophic scar fibroblasts(HSF)through the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway.Methods HSF were isolated from human hypertrophic scar tissue and cultured in vitro.Cells were allocated to the following groups:Control,luteolin low dose,luteolin high dose,luteolin high dose+Colivelin(a JAK2/STAT3 activator),and AG490(a JAK2/STAT3 pathway inhibitor).Cell proliferation was assessed by MTT assay;migration and invasion by Transwell assays;apoptosis by flow cytometry;JAK2 and STAT3 mRNA levels by real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR);and protein expression of type Ⅰ collagen(Col-Ⅰ),Col-Ⅲ,alpha-smooth muscle actin(α-SMA),Ki-67,caspase-3,p-JAK2,JAK2,p-STAT3,and STAT3 by Western blot.Results Relative to the Control group,luteolin low-dose,luteolin high-dose,and AG490 treatments significantly reduced HSF proliferation rate,numbers of migrating and invading cells,JAK2 and STAT3 mRNA,Col-Ⅰ,Col-Ⅲ,α-SMA,Ki-67,and the phosphorylation ratios p-JAK2/JAK2 and p-STAT3/STAT3(P＜0.05).Apoptosis rate and caspase-3 protein expression were significantly increased in these groups(P＜0.05).Colivelin partially reversed luteolin's inhibitory effects on HSF(P＜0.05).No significant differences were observed between the AG490 group and the luteolin high-dose group(P＞0.05).Conclusion Luteolin suppresses proliferation and migration and promotes apoptosis of HSF.These effects are likely mediated,at least in part,by inhibition of the JAK2/STAT3 signaling pathway.