Tofatinib inhibits skin fibrosis in systemic sclerosis mice via JAK/STAT pathway
To explore the inhibitory effect of tofatinib on skin fibrosis in bleomycin-induced systemic sclerosis mice and its mechanism,total of 24 Balb/c mice were recruited and divided into blank group,model group,early intervention group and late intervention group.The model group and two intervention groups were subcutaneously injected with bleomycin to induce model of systemic sclerosis,while the blank group was subcutaneously injected with normal saline.The early intervention group was given tofatinib intervention starting from the modeling process,and the late intervention group was given tofatinib intervention on the 8th day after the modeling process.HE and Masson staining were used to observe lesion tissue;ELISA was used to detect of serum level of IL-6;hydrolysis was employed to detect the hydroxyproline content;RT-PCR was used to measure the mRNA expression levels of p-JAK1,p-JAK2,p-JAK3 and p-STAT3;and Westem blot was used to detect the expression levels of p-JAK1,p-JAK2,p-JAK3,p-STAT3,type I collagen fiber and A-smooth muscle proteins.Compared with the blank group,the dermis in model group was thicker and collagen fibers were increased.After tofacatib intervention,the dermis was thinned and collagen fibers were relatively reduced.The dermis in early intervention group was thinner than that in late intervention group(P＜0.05).The level of IL-6 in late intervention group was significantly lower compared with that in model group(P＜0.05).The mRNA expressions of P-JAK2 and P-JAK3 in early intervention group were lower compared with those in model group(P＜0.05),and the protein expressions of P-JAK1,P-JAK3 and P-STAT3 in early intervention group were lower compared with those in model group(P＜0.05).The expression of P-JAK1 protein in early intervention group was lower than that in late intervention group(P＜0.05).In conclusion,tofatinib can suppress skin fibrosis in mice with systemic sclerosis by inhibiting JAK/STAT signaling pathway,and the anti-fibrosis effect of early tofatinib intervention is more obvious.
万方数据
维普
