Trigonelline hydrochloride attenuates silica-induced pulmonary fibrosis by orchestrating fibroblast to myofibroblast differentiation

作者：Fengqin Zhang, Huihui Yue, Ruihan Dong, Jianhan He, Ling Zhou, Xinran Dou, L. Wang, Pengdou Zheng, Zhenyu Mao, Xiaoyan Zhu, Yi Wang, Huiguo Liu, Huilan Zhang · 发表于：Respiratory Research · 年份：2024 · DOI：10.1186/s12931-024-02876-1 · 被引用次数：11 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Occupational and environmental lung diseases、Occupational exposure and asthma

Abstract Background 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. Methods 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. Results In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO 2 -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 2 group. In terms of mechanism, we obtained in vitro evidence that Tri...