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低温直接作用于骨骼肌细胞并增加IL-6的表达

刘奔¹, 修雯靖¹, 段进杰¹, 王春炅^1,2,*

¹天津医科大学基础医学院生理学与病理生理学系，天津 300070；² 天津医科大学护理学院，天津 300070

摘要

在环境温度降低时，骨骼肌可通过寒颤和非寒颤产热维持体温。除了神经体液调节，有研究表明脂肪细胞可直接对低温产生反应而增加产热，提示机体对寒冷刺激存在自身调节。但骨骼肌是否存在不依赖于神经体液调节机制而直接对低温起反应的自身调节还未知。瞬时受体电位通道TRPM8和TRPA1是机体感受寒冷的关键蛋白。本研究通过RT-PCR发现，小鼠骨骼肌组织及离体培养的C2C12肌管细胞可表达TRPM8。将C2C12肌管细胞置于33 °C低温环境培养6 h后，转录组学表明低温可改变骨骼肌细胞众多基因表达。通过KEGG-Pathway富集分析发现，低温刺激可改变IL-17、TNFα、MAPK、FoxO、Hedgehog、Hippo、Toll-like receptor、Notch、Wnt等重要信号通路。蛋白网络互作分析显示IL-6基因是骨骼肌细胞受低温直接影响的关键基因。进一步研究发现，33 °C低温环境培养可增加C2C12肌管IL-6 mRNA及蛋白质表达。本研究结果表明，骨骼肌细胞对低温刺激存在自身调节，低温可直接上调骨骼肌细胞IL-6的表达。

关键词： 骨骼肌细胞; 低温刺激; 白介素-6; 瞬时受体电位通道M8

Low temperature exposure increases IL-6 expression in skeletal muscle cells

LIU Ben¹, XIU Wen-Jing¹, DUAN Jin-Jie¹, WANG Chun-Jiong^1,2,*

¹Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin 300070, China；²School of Nursing, Tianjin Medical University, Tianjin 300070, China

Abstract

The shivering and nonshivering thermogenesis in skeletal muscles is important for maintaining body temperature in a cold environment. In addition to nervous-humoral regulation, adipose tissue was demonstrated to directly respond to cold in a cell-autonomous manner to produce heat. However, whether skeletal muscle can directly respond to low temperature in an autoregulatory manner is unknown. Transient receptor potential (TRP) channels TRPM8 and TRPA1 are two important cold sensors. In the current study, we found TRPM8 was expressed in mouse skeletal muscle tissue and C2C12 myotubes by RT-PCR. After exposure to 33 °C for 6 h, the gene expression pattern of C2C12 myotubes was significantly changed which was evidenced by RNA-sequencing. KEGG-Pathway enrichment analysis of these differentially expressed genes showed that low temperature changed several important signaling pathways, such as IL-17, TNFα, MAPK, FoxO, Hedgehog, Hippo, Toll-like receptor, Notch, and Wnt signaling pathways. Protein-protein interaction network analysis revealed that IL-6 gene was a key gene which was directly affected by low temperature in skeletal muscle cells. In addition, both mRNA and protein levels of IL-6 were increased by 33 °C exposure in C2C12 myotubes. In conclusion, our findings demonstrated that skeletal muscle cells could directly respond to low temperature, characterized by upregulated expression of IL-6 in skeletal muscle cells.

Key words: skeletal muscle cells; low temperature; IL-6; TRPM8

收稿日期：　　录用日期：

通讯作者：王春炅　　E-mail: wangchunjiong@tmu.edu.cn

DOI: 10.13294/j.aps.2022.0022

引用本文：

刘奔, 修雯靖, 段进杰, 王春炅. 低温直接作用于骨骼肌细胞并增加IL-6的表达[J]. 生理学报 2022; 74 (2): 201-208.

LIU Ben, XIU Wen-Jing, DUAN Jin-Jie, WANG Chun-Jiong. Low temperature exposure increases IL-6 expression in skeletal muscle cells. Acta Physiol Sin 2022; 74 (2): 201-208 (in Chinese with English abstract).