HMGB1 RNAi inhibits α-smooth muscle actin expression in mice with bleomycin-induced lung fibrosis

The high mobility group B1(HMGB1) is a nuclear protein that is present in almost all eukaryotic cells and is highly conserved between species.In this study,we aimed to investigate the effect of down-regulating HMGB1 expression by RNAi on the expression of α-smooth muscle actin(α-SMA) in mice with lung fibrosis induced by bleomycin.Forty C57BL/c male mice aged from 4 to 6 weeks were randomly divided into control group,bleomycin group,bleomycin plus HMGB1 RNAi group,and RNAi negative control group.Bleomycin group were treated with bleomycin(3 mg/ kg) via endotracheally injection on day 0,while control group were treated with PBS.And bleomycin plus HMGB1 RNAi group were received HMGB1 siRNA plus bleomycin intratracheal administration.RNAi negative control group were received negative siRNA plus bleomycin intratracheal administration.Mice were sacrificed at day 10 after the treatments.The lung tissue was examined with HE staining and Masson staining for pathological changes,and also detected by immunohistochemistry for HMGB1 and α-SMA expresion.The mRNA expression of HMGB1 and α-SMA was detected by reverse transcriptase-polymerase chain reaction(RT-PCR).Histological examination of lung specimens demonstrated that HMGB1 siRNA administration lessened bleomycin-induced lung fibrosis and significantly reduced collagen accumulation.HMGB1 mRNA and protein expression in HMGB1 siRNA-treated mice was significantly decreased(P 0.01).The expression levels of α-SMA mRNA and protein were also inhibited by HMGB1 RNAi treatment in mice with intratracheal administration of bleomycin(P 0.01).In conclusion,HMGB1 RNAi alleviate the bleomycin-induced lung fibrosis by downregulating the expression of α-SMA.