Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul 05368, Korea.
Core Research Laboratory, Medical Science Research Institute, Kyung Hee University Hospital at Gangdong, Seoul 05278, Korea.
BMB Rep. 2024 Mar;57(3):143-148. doi: 10.5483/BMBRep.2023-0099.
Pulmonary fibrosis is a serious lung disease that occurs predominantly in men. Genistein is an important natural soybeanderived phytoestrogen that affects various biological functions, such as cell migration and fibrosis. However, the antifibrotic effects of genistein on pulmonary fibrosis are largely unknown. The antifibrotic effects of genistein were evaluated using in vitro and in vivo models of lung fibrosis. Proteomic data were analyzed using nano-LC-ESI-MS/MS. Genistein significantly reduced transforming growth factor (TGF)-β1-induced expression of collagen type I and α-smooth muscle actin (SMA) in MRC-5 cells and primary fibroblasts from patients with idiopathic pulmonary fibrosis (IPF). Genistein also reduced TGF-β1-induced expression of p-Smad2/3 and p-p38 MAPK in fibroblast models. Comprehensive protein analysis confirmed that genistein exerted an anti-fibrotic effect by regulating various molecular mechanisms, such as unfolded protein response, epithelial mesenchymal transition (EMT), mammalian target of rapamycin complex 1 (mTORC1) signaling, cell death, and several metabolic pathways. Genistein was also found to decrease hydroxyproline levels in the lungs of BLM-treated mice. Genistein exerted an anti-fibrotic effect by preventing fibroblast activation, suggesting that genistein could be developed as a pharmacological agent for the prevention and treatment of pulmonary fibrosis. [BMB Reports 2024; 57(3): 143-148].
肺纤维化是一种主要发生在男性中的严重肺部疾病。染料木黄酮是一种重要的天然大豆来源的植物雌激素，它影响多种生物学功能，如细胞迁移和纤维化。然而，染料木黄酮对肺纤维化的抗纤维化作用在很大程度上是未知的。使用肺纤维化的体外和体内模型评估了染料木黄酮的抗纤维化作用。使用纳升液相色谱-电喷雾-串联质谱法（nano-LC-ESI-MS/MS）分析蛋白质组学数据。染料木黄酮显著降低了转化生长因子（TGF）-β1诱导的 MRC-5 细胞和特发性肺纤维化（IPF）患者原代成纤维细胞中 I 型胶原和α-平滑肌肌动蛋白（SMA）的表达。染料木黄酮还降低了成纤维细胞模型中 TGF-β1 诱导的 p-Smad2/3 和 p-p38 MAPK 的表达。综合蛋白质分析证实，染料木黄酮通过调节各种分子机制发挥抗纤维化作用，如未折叠蛋白反应、上皮间质转化（EMT）、雷帕霉素靶蛋白复合物 1（mTORC1）信号、细胞死亡和几种代谢途径。还发现染料木黄酮可降低博莱霉素处理的小鼠肺部的羟脯氨酸水平。染料木黄酮通过防止成纤维细胞活化发挥抗纤维化作用，表明染料木黄酮可开发为预防和治疗肺纤维化的药物。[BMB 报告 2024；57(3): 143-148]。
