Cheng Ge, Zhang Zifang, Wang Yixuan, Zao Youjiao, Wang Ruoqi, Gao Mengying, Feng Miaomiao, Zhang Xi, Jiang Peng
Department of Pathogen Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Int J Mol Sci. 2023 Oct 9;24(19):15003. doi: 10.3390/ijms241915003.
() muscle larvae colonize in the host's skeletal muscle cells, which are surrounded by collagen capsules. The mechanism underlying muscle stage larva-induced collagen capsule formation remains unknown. To clarify the mechanism, a muscular-infected mouse model was established by a single lateral tail vein injection with 20,000 newborn larvae (NBL). The infected mice were treated with or without SB525334 (TGF-β1 receptor type I inhibitor). Diaphragms were obtained post-infection, and the expression levels of the TGF-β1/Smad3 pathway-related genes and collagen genes (type IV and VI) were observed during the process of collagen capsule formation. The changes in myoblasts under stimulation of the excretory-secretory (ES) products of NBL with or without SB525334 were further investigated. Results showed that the expression levels of type IV collagen gene, type VI collagen gene, and were significantly increased in infected mice muscle cells. The expression levels of all the above genes were enhanced by the products of NBL in myoblast cells. These changes were reversed by co-treatment with SB525334 in vivo and in vitro. In conclusion, the TGF-β1/Smad3 pathway can be activated by infection in muscle cells. The activated TGF-β1/Smad3 pathway can stimulate the secretion of collagens by myocytes and plays a promoting role in the process of collagen capsule formation. The research has the limitation that the protein identification of the products of NBL has yet to be performed. Therefore, the specific components in the ES products that induce collagen synthesis should be further investigated.
（）肌肉幼虫定殖于宿主的骨骼肌细胞中，这些细胞被胶原胶囊包围。肌肉期幼虫诱导胶原胶囊形成的潜在机制尚不清楚。为了阐明该机制，通过单次经侧尾静脉注射20,000只新生幼虫（NBL）建立了肌肉感染小鼠模型。对感染的小鼠给予或不给予SB525334（I型TGF-β1受体抑制剂）治疗。感染后获取膈肌，观察胶原胶囊形成过程中TGF-β1/Smad3信号通路相关基因和胶原基因（IV型和VI型）的表达水平。进一步研究了在有或无SB525334的情况下，NBL排泄分泌（ES）产物刺激下成肌细胞的变化。结果显示，感染小鼠肌肉细胞中IV型胶原基因、VI型胶原基因的表达水平显著升高。上述所有基因的表达水平在成肌细胞中均被NBL产物增强。体内和体外联合使用SB525334可逆转这些变化。总之，TGF-β1/Smad3信号通路可被肌肉细胞感染激活。激活的TGF-β1/Smad3信号通路可刺激肌细胞分泌胶原蛋白，并在胶原胶囊形成过程中起促进作用。该研究的局限性在于尚未对NBL产物进行蛋白质鉴定。因此，应进一步研究ES产物中诱导胶原合成的具体成分。
