Department of Respiratory and Critical Care Medicine, National Health Commission Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.
Respir Res. 2024 Jun 15;25(1):242. doi: 10.1186/s12931-024-02876-1.
Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical dilemmas due to limited effective treatment options available. Trigonelline (Trig), a plant alkaloid extracted mainly from coffee and fenugreek, have diverse biological properties such as protecting dermal fibroblasts against ultraviolet radiation and has the potential to inhibit collagen synthesis. However, it's unclear whether Trig inhibits fibroblast activation to attenuate silicosis-induced pulmonary fibrosis is unclear.
To evaluate the therapeutic efficacy of Trig in the context of silicosis-related pulmonary fibrosis, a mouse model of silicosis was utilized. The investigation seeks to elucidated Trig's impact on the progression of silica-induced pulmonary fibrosis by evaluating protein expression, mRNA levels and employing Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red staining. Subsequently, we explored the mechanism underlying of its functions.
In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO-induced silicosis and BLM-induced pulmonary fibrosis, as evidenced by improved histochemical staining and reduced fibrotic marker expressions. Additionally, we showed that the differentiation of fibroblast to myofibroblast was imped in Trig + SiO group. In terms of mechanism, we obtained in vitro evidence that Trig inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-β/Smad signaling according to the in vitro evidence. Notably, our finding indicated that Trig seemed to be safe in mice and fibroblasts.
In summary, Trig attenuated the severity of silicosis-related pulmonary fibrosis by alleviating the differentiation of myofibroblasts, indicating the development of novel therapeutic approaches for silicosis fibrosis.
矽肺是一种全球范围内的主要职业健康危害，其发病率、患病率和死亡率呈上升趋势，由于可用的有效治疗选择有限，因此带来了巨大的临床难题。植物生物碱六氢吡啶（Trig）主要从咖啡和胡芦巴中提取，具有多种生物学特性，如保护皮肤成纤维细胞免受紫外线辐射，并具有抑制胶原合成的潜力。然而，尚不清楚 Trig 是否抑制成纤维细胞活化以减轻矽肺引起的肺纤维化。
为了评估 Trig 在矽肺相关肺纤维化中的治疗效果，使用了矽肺小鼠模型。研究旨在通过评估蛋白表达、mRNA 水平以及使用苏木精和伊红（H&E）、马松三色和天狼星红染色来阐明 Trig 对二氧化硅诱导的肺纤维化进展的影响。随后，我们探讨了其功能的机制。
体内实验表明，Trig 显著减轻了 SiO 诱导的矽肺和 BLM 诱导的肺纤维化，表现在组织化学染色改善和纤维化标志物表达减少。此外，我们表明 Trig 在 Trig+SiO 组中阻止了成纤维细胞向肌成纤维细胞的分化。在机制方面，我们根据体外证据获得了 Trig 通过抑制 TGF-β/Smad 信号通路抑制成纤维细胞向肌成纤维细胞分化的体外证据。值得注意的是，我们的发现表明 Trig 在小鼠和纤维母细胞中似乎是安全的。
综上所述，Trig 通过减轻肌成纤维细胞的分化减轻了矽肺相关肺纤维化的严重程度，表明开发了针对矽肺纤维化的新治疗方法。
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