Department of Human Functional Genomics, Advanced Science Research Promotion Center, Organization for the Promotion of Regional Innovation, Mie University, 1577 Kurima-machiya, Tsu, Mie, 514-8507, Japan.
Department of Genome Analysis, Institute of Biomedical Science, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
J Physiol Anthropol. 2021 Oct 22;40(1):16. doi: 10.1186/s40101-021-00267-9.
Physiological thermoregulatory systems in humans have been a key factor for adaptation to local environments after their exodus from Africa, particularly, to cold environments outside Africa. Recent studies using high-throughput sequencing have identified various genes responsible for cold adaptation. However, the molecular mechanisms underlying initial thermoregulation in response to acute cold exposure remain unclear. Therefore, we investigated transcriptional profiles of six young Japanese male adults exposed to acute cold stress.
In a climatic chamber, the air temperature was maintained at 28°C for 65 min and was then gradually decreased to 19°C for 70 min. Saliva samples were obtained from the subjects at 28°C before and after 19°C cold exposure and were used for RNA sequencing.
In the cold exposure experiment, expression levels of 14 genes were significantly changed [false discovery rate (FDR) < 0.05] although the degree of transcriptional changes was not high due to experimental conditions or blunted transcriptional reaction in saliva to cold stress. As a result, differential gene expression analyses detected the cathepsin L (CTSL) gene to be significantly upregulated, with FDR < 0.05 and log fold change value > 1; thus, this gene was identified as a differentially expressed gene. Given that the cathepsin L protein is related to invasion of the novel coronavirus (SARS-CoV-2), mild cold stress might alter the susceptibility to coronavirus disease-19 in humans. The gene ontology enrichment analysis for 14 genes with FDR < 0.05 suggested that immune-related molecules could be activated by mild cold stress.
The results obtained from this study indicate that CTSL expression levels can be altered by acute mild cold stress.
人类的生理体温调节系统是其走出非洲后适应当地环境的关键因素，尤其是适应非洲以外的寒冷环境。最近使用高通量测序的研究已经确定了各种负责冷适应的基因。然而，对于急性冷暴露后初始体温调节的分子机制仍不清楚。因此，我们研究了 6 名年轻日本男性在急性冷应激下的转录谱。
在气候室内，空气温度维持在 28°C 65 分钟，然后逐渐降至 19°C 70 分钟。在 28°C 和 19°C 冷暴露前后从受试者中采集唾液样本，并进行 RNA 测序。
在冷暴露实验中，尽管由于实验条件或唾液对冷应激的转录反应迟钝，转录变化程度不高，但有 14 个基因的表达水平显著变化[错误发现率（FDR）<0.05]。结果，差异基因表达分析检测到组织蛋白酶 L（CTSL）基因显著上调，FDR<0.05 和对数倍变化值>1；因此，该基因被鉴定为差异表达基因。鉴于组织蛋白酶 L 蛋白与新型冠状病毒（SARS-CoV-2）的入侵有关，轻度冷应激可能会改变人类对冠状病毒病-19 的易感性。FDR<0.05 的 14 个基因的基因本体富集分析表明，轻度冷应激可以激活免疫相关分子。
本研究结果表明，急性轻度冷应激可以改变 CTSL 的表达水平。
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