Division of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India.
Division of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, India.
J Nutr Biochem. 2023 Jun;116:109294. doi: 10.1016/j.jnutbio.2023.109294. Epub 2023 Mar 21.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disorder that severely impairs lung function, by increasing lung stiffness. Sesamol, a phenolic Phyto-molecule isolated from sesame seeds, possess a rich source of protein and is known to have extensive nutritional and health effects. Here we investigated the effect of sesamol on TGF-β/periostin-induced fibroblast differentiation in in vitro and bleomycin-induced pulmonary fibrosis in an in vivo model. Our results demonstrated that activation of (DHLF, LL29, NHLF and A549) cells with TGF-β, elevates the epithelial to mesenchymal transition, extracellular matrix, and collagen deposition and periostin signaling marker's expression, further treatment with sesamol attenuated these markers significantly. In addition, sesamol treatment improved the TGF-β-induced contraction and migration of cells. Mechanistic studies showed that activation of IPF cells with periostin increased the TGF-β signaling and treatment with sesamol significantly abrogated the periostin-induced TGF-β activation and its downstream fibrotic marker's expression. In in vivo, sesamol treatment attenuated the lung inflammation, infiltration of cells, wall thickening and the formation of fibrous bands significantly in BLM-induced fibrosis rats. Molecular studies revealed that sesamol treatment reduced the bleomycin-induced fibrotic, inflammatory, apoptotic marker's expression by modulating the TGF-β/periostin crosstalk signaling in a dose-dependent manner. Further, treatment with sesamol dramatically improved lung function and decreased mortality. Our study first time reports the sesamol's inhibitory effects on periostin signalling. Collectively, our study demonstrated that periostin and TGF-β seem to work in a positive-feedback loop, inducing the other, therefore, targeting TGF-β/periostin signaling may provide a better therapeutic approach against IPF and other fibrotic disorders.
特发性肺纤维化（IPF）是一种慢性进行性疾病，通过增加肺的僵硬度来严重损害肺功能。芝麻酚是一种从芝麻种子中分离出来的酚类植物分子，含有丰富的蛋白质，具有广泛的营养和健康作用。在这里，我们研究了芝麻酚对 TGF-β/periostin 诱导的体外成纤维细胞分化和博莱霉素诱导的肺纤维化模型中的作用。我们的结果表明，TGF-β激活（DHLF、LL29、NHLF 和 A549）细胞后，上皮间质转化、细胞外基质和胶原沉积以及 periostin 信号标志物的表达增加，进一步用芝麻酚处理可显著减弱这些标志物。此外，芝麻酚处理可改善 TGF-β诱导的细胞收缩和迁移。机制研究表明，periostin 激活 IPF 细胞增加了 TGF-β信号，芝麻酚处理显著阻断了 periostin 诱导的 TGF-β激活及其下游纤维化标志物的表达。在体内，芝麻酚治疗可显著减轻 BLM 诱导纤维化大鼠的肺炎症、细胞浸润、壁增厚和纤维带形成。分子研究表明，芝麻酚通过调节 TGF-β/periostin 串扰信号，以剂量依赖性方式降低博莱霉素诱导的纤维化、炎症、凋亡标志物的表达，从而改善肺功能并降低死亡率。我们的研究首次报道了芝麻酚对 periostin 信号的抑制作用。总之，我们的研究表明 periostin 和 TGF-β似乎在正反馈环中协同作用，诱导对方，因此靶向 TGF-β/periostin 信号可能为 IPF 和其他纤维化疾病提供更好的治疗方法。
