Zhang Xinxin, Xie Yizi, Cai Yan, Huang Huiting, Liang Huiqiu, Liao Gang, Jiang Yong, Peng Xiaoyun, Zhan Shaofeng, Huang Xiufang
The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.
The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.
Food Funct. 2024 Dec 9;15(24):12193-12209. doi: 10.1039/d4fo01474j.
Idiopathic pulmonary fibrosis (IPF) is a chronic age-related lung disease with a high mortality rate. Kaempferol (KMP), an active ingredient in common plants and foods with anti-inflammatory, antioxidant and immunomodulatory properties, has been shown to be effective against fibrotic diseases. However, the molecular mechanisms underlying the treatment of IPF with KMP remain unclear. Therefore, IPF mice were established by intratracheal instillation of bleomycin (BLM) to explore the efficacy and underlying mechanism of KMP in the treatment of IPF. We found that KMP improved the body weight changes of BLM-induced IPF mice, alleviated inflammatory infiltration and collagen deposition, and decreased the expression levels of hydroxyproline, , , , , , , , , and , while up-regulating the expression in lung tissues. The transcriptomic results showed that KMP may exert therapeutic effects against IPF by regulating the PPARG/TNC signaling pathway to reduce extracellular matrix (ECM) deposition. Interestingly, ROC curve analysis suggested that TNC and PPARG had good diagnostic performance for IPF, and TF prediction revealed that PPARG is an important upstream gene regulating TNC, and the IF experiment confirmed the co-localization of TNC and PPARG. Molecular docking showed that KMP bound well to PPARG and TNC, and IF results revealed that KMP significantly reduced the interaction between PPARG and TNC. Furthermore, RT-PCR, WB, IHC and IF experiments confirmed that KMP elevated the expression of PPARG and inhibited the expression of TNC, thus inhibiting the ECM-receptor interaction pathway and ultimately serving as a therapeutic treatment for IPF mice. These findings revealed that KMP reduced inflammatory infiltration and collagen deposition in the lungs of IPF mice and that the PPARG/TNC signaling pathway may be an important mechanism for the treatment of IPF with KMP, which provides a new perspective for the development of therapeutic approaches for IPF.
特发性肺纤维化（IPF）是一种与年龄相关的慢性肺部疾病，死亡率很高。山奈酚（KMP）是常见植物和食物中的一种活性成分，具有抗炎、抗氧化和免疫和免疫调节特性，已被证明对纤维化疾病有效。然而，KMP治疗IPF的分子机制仍不清楚。因此，通过气管内注射博来霉素（BLM）建立IPF小鼠模型，以探讨KMP治疗IPF的疗效及潜在机制。我们发现，KMP改善了BLM诱导的IPF小鼠的体重变化，减轻了炎症浸润和胶原沉积，并降低了羟脯氨酸、……（此处原文缺失部分内容）以及……（此处原文缺失部分内容）的表达水平，同时上调了肺组织中……（此处原文缺失部分内容）的表达。转录组学结果表明，KMP可能通过调节PPARG/TNC信号通路减少细胞外基质（ECM）沉积，从而对IPF发挥治疗作用。有趣的是，ROC曲线分析表明，TNC和PPARG对IPF具有良好的诊断性能，转录因子预测显示PPARG是调节TNC的重要上游基因，免疫荧光实验证实了TNC和PPARG的共定位。分子对接显示KMP与PPARG和TNC结合良好，免疫荧光结果显示KMP显著降低了PPARG与TNC之间的相互作用。此外，逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法（WB）、免疫组织化学（IHC）和免疫荧光实验证实，KMP上调了PPARG的表达并抑制了TNC的表达，从而抑制了ECM-受体相互作用途径，最终对IPF小鼠起到治疗作用。这些发现表明，KMP减少了IPF小鼠肺部的炎症浸润和胶原沉积，PPARG/TNC信号通路可能是KMP治疗IPF的重要机制，这为IPF治疗方法的开发提供了新的视角。
