Makrufardi Firdian, Peng Syue-Wei, Chung Kian Fan, Chadeau-Hyam Marc, Lee Kang-Yun, Hsiao Ta-Chih, Ho Kin-Fai, Rusmawatiningtyas Desy, Murni Indah Kartika, Arguni Eggi, Wang Yuan-Hung, Ho Shu-Chuan, Yang Feng-Ming, Chuang Kai-Jen, Lin Sheng-Chieh, Chuang Hsiao-Chi
International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Department of Child Health, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada - Dr. Sardjito Hospital, Yogyakarta, Indonesia.
Front Med (Lausanne). 2025 Apr 17;12:1531154. doi: 10.3389/fmed.2025.1531154. eCollection 2025.
The objective of this study was to examine the effects of extreme temperatures on the gene signature and pathways of airway epithelial cells in mice and asthma patients.
We investigated the effects of temperature exposure at normal (22°C), and extreme low (10°C), high (40°C) and temperature fluctuation (40°C for 2 h followed by 10°C for next 2 h) in B6.-D mice and pediatric and adult patient's airway epithelial exposed to extreme temperatures.
We observed that Mmp8, Sftpb, Cxcl15 and Cd14 were significantly upregulated in airway epithelial cells in mice model. Cma1, Kit, Fdx1, Elf1a, Cdkn2aipnl, Htatsf1, Mfsd13a, Gtf2h5, Tiam2, and Trmt10c were significantly upregulated in 40°C exposure in airway epithelial cells. Sftpc, Gpr171, Sic34a2, Cox14, Lamp3, Luc7l, Nxnl, Tmub2, Tob1, and Cd3e genes were significantly upregulated in 10°C exposure group. Pediatric asthma subjects in the extreme high temperature group consistently showed decreased Wfdc21, Cib3, and Sftpc, at the same time increased Tiam2 and Cma1 expression, while in the extreme low temperature group exhibited consistently higher expression of Sftpc and Nxnl, at the same time decreased Wfdc21, Cib3, Cma1, and Dld expression. Notably, the mice in the extreme temperature fluctuation group showed decreased Wfdc21, Cib3, Gpr171, and Cttnbp2 expression, while increased Hbb-bs expression. Adult asthma subjects in the extreme temperature fluctuation group showed consistently decreased Wfdc21, Cib3, Gpr171, and Cttnbp2 expression, while increased Tiam2 and Cma1 expression. We observed that the mild, moderate, and severe asthma subject in the extreme low temperature group showed increased Tob1, Mub2, Sic34a2, Sftpc, Nxnl, Luc71, Lamp3, Gpr171, Cox14, and Cd3e expression, while in the severe asthma subjects showed increased expression in all temperature exposure group.
Our study highlights the effects of extreme temperatures on the gene signature of the airway epithelium in both mice and asthma patients. These findings suggest that extreme temperatures modulate gene expression in the airway epithelium, potentially serving as clinical indicators or biomarkers in response to climate change.
本研究的目的是检测极端温度对小鼠和哮喘患者气道上皮细胞的基因特征及信号通路的影响。
我们研究了正常温度(22°C)、极端低温(10°C)、极端高温(40°C)以及温度波动(先40°C暴露2小时,随后10°C暴露2小时)对B6.-D小鼠以及儿科和成年患者暴露于极端温度下的气道上皮细胞的影响。
我们观察到在小鼠模型中,气道上皮细胞中的Mmp8、Sftpb、Cxcl15和Cd14显著上调。在气道上皮细胞40°C暴露组中,Cma1、Kit、Fdx1、Elf1a、Cdkn2aipnl、Htatsf1、Mfsd13a、Gtf2h5、Tiam2和Trmt10c显著上调。在10°C暴露组中,Sftpc、Gpr171、Sic34a2、Cox14、Lamp3、Luc7l、Nxnl、Tmub2、Tob1和Cd3e基因显著上调。极端高温组中的儿科哮喘受试者持续表现出Wfdc21、Cib3和Sftpc表达降低,同时Tiam2和Cma1表达增加,而在极端低温组中则持续表现出Sftpc和Nxnl表达较高,同时Wfdc21、Cib3、Cma1和Dld表达降低。值得注意的是,极端温度波动组中的小鼠表现出Wfdc21、Cib3、Gpr171和Cttnbp2表达降低,而Hbb-bs表达增加。极端温度波动组中的成年哮喘受试者持续表现出Wfdc21、Cib3、Gpr171和Cttnbp2表达降低,而Tiam2和Cma1表达增加。我们观察到极端低温组中的轻度、中度和重度哮喘受试者表现出Tob1、Mub2、Sic34a2、Sftpc、Nxnl、Luc71、Lamp3、Gpr171、Cox14和Cd3e表达增加,而重度哮喘受试者在所有温度暴露组中均表现出表达增加。
我们的研究突出了极端温度对小鼠和哮喘患者气道上皮基因特征的影响。这些发现表明,极端温度可调节气道上皮中的基因表达,有可能作为应对气候变化的临床指标或生物标志物。