Li Jian, Wang Gang, Sun Xia
Jinan Centre for Disease Control and Prevention, Jinan, Shandong 250001, P.R. China.
Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical college, Xuzhou, Jiangsu 223002, P.R. China.
Int J Mol Med. 2014 Nov;34(5):1219-24. doi: 10.3892/ijmm.2014.1916. Epub 2014 Aug 27.
β-catenin contributes to the pathogenesis of lung fibrosis. However, the expression of β-catenin in fibroblasts under fibrotic conditions has not been studied. We investigated the expression of β-catenin in lung fibroblasts from bleomycin (BLM)‑challenged mice and human lung fibroblasts treated with transforming growth factor β (TGF-β) or lysophosphatidic acid (LPA) by western blot analysis. The result showed that the expression of β-catenin was significantly increased in lung fibrotic foci and lung fibroblasts from bleomycin‑challenged mice. TGF-β stimulated β-catenin expression and induced differentiation in human lung fibroblasts in vitro. Pretreatment of the NF-κB activation inhibitor attenuated the TGF-β‑induced expression of β-catenin and differentiation in human lung fibroblasts. Similarly, LPA induced β-catenin expression in human lung fibroblasts, and pre-treatment of the neutralized anti-TGF-β antibody attenuated the LPA‑induced expression of β-catenin and differentiation in human lung fibroblasts. The results suggested that β-catenin expression is upregulated in lung fibroblast during differentiation, and that TGF-β induced β-catenin expression in human lung fibroblasts through the activation of NF-κB.
β-连环蛋白参与肺纤维化的发病机制。然而,纤维化条件下成纤维细胞中β-连环蛋白的表达尚未得到研究。我们通过蛋白质印迹分析研究了博来霉素(BLM)攻击小鼠的肺成纤维细胞以及用转化生长因子β(TGF-β)或溶血磷脂酸(LPA)处理的人肺成纤维细胞中β-连环蛋白的表达。结果显示,在博来霉素攻击小鼠的肺纤维化病灶和肺成纤维细胞中,β-连环蛋白的表达显著增加。TGF-β刺激人肺成纤维细胞中β-连环蛋白的表达并在体外诱导其分化。NF-κB激活抑制剂预处理减弱了TGF-β诱导的人肺成纤维细胞中β-连环蛋白的表达和分化。同样,LPA诱导人肺成纤维细胞中β-连环蛋白的表达,而中和的抗TGF-β抗体预处理减弱了LPA诱导的人肺成纤维细胞中β-连环蛋白的表达和分化。结果表明,在分化过程中肺成纤维细胞中β-连环蛋白表达上调,并且TGF-β通过激活NF-κB诱导人肺成纤维细胞中β-连环蛋白的表达。