Department of Geriatrics, Chongqing Medical University, Chongqing, 400010, China.
Department of Geriatrics, Chongqing General Hospital, Chongqing, 400010, China.
Adv Rheumatol. 2023 Aug 28;63(1):45. doi: 10.1186/s42358-023-00325-z.
The study explored improvements in pulmonary inflammation and fibrosis in a bovine type II collagen-induced rheumatoid arthritis-associated interstitial lung disease mouse model after treatment with baricitinib and the possible mechanism of action.
A rheumatoid arthritis-associated interstitial lung disease mouse model was established, siRNA Jak2 and lentiviral vectors were transfected with human embryonic lung fibroblast cells. And the levels of relevant proteins in mouse lung tissue and human embryonic lung fibroblasts were detected by Western blotting.
The levels of JAK2, p-JAK2, p-STAT3, p-SMAD3, SMA, TGFβR2, FN and COL4 were increased in the lung tissues of model mice (P < 0.5) and decreased after baricitinib intervention (P < 0.05). The expression levels of p-STAT3, p-SMAD3, SMA, TGFβR2, FN and COL4 were reduced after siRNA downregulation of the JAK2 gene (P < 0.01) and increased after lentiviral overexpression of the JAK2 gene (P < 0.01).
Baricitinib alleviated fibrosis in the lung tissue of rheumatoid arthritis-associated interstitial lung disease mice, and the mechanism of action may involve the downregulation of Smad3 expression via inhibition of the Jak2/Stat3 signaling pathway, with consequent inhibition of the profibrotic effect of transforming growth factor-β1.
研究巴瑞替尼治疗牛Ⅱ型胶原诱导的类风湿关节炎相关间质性肺疾病小鼠模型后对肺炎症和纤维化的改善作用，并探讨其可能的作用机制。
建立类风湿关节炎相关间质性肺疾病小鼠模型，用 siRNAJak2 和慢病毒载体转染人胚肺成纤维细胞，用 Western blot 法检测小鼠肺组织和人胚肺成纤维细胞中相关蛋白的水平。
模型小鼠肺组织中 JAK2、p-JAK2、p-STAT3、p-SMAD3、SMA、TGFβR2、FN 和 COL4 水平升高（P<0.05），巴瑞替尼干预后降低（P<0.05）。JAK2 基因 siRNA 下调后 p-STAT3、p-SMAD3、SMA、TGFβR2、FN 和 COL4 表达水平降低（P<0.01），JAK2 基因慢病毒过表达后表达水平升高（P<0.01）。
巴瑞替尼减轻了类风湿关节炎相关间质性肺疾病小鼠肺组织的纤维化，其作用机制可能涉及通过抑制 Jak2/Stat3 信号通路下调 Smad3 表达，从而抑制转化生长因子-β1 的促纤维化作用。
