NOD-like receptors mediate inflammatory lung injury during plateau hypoxia exposure
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(2020) 39:32
ORIGINAL ARTICLE
Open Access
NOD-like receptors mediate inflammatory lung injury during plateau hypoxia exposure Haiyan Wang1, Xue Lin1 and Xiaoyan Pu1,2*
Abstract Background: The lung is an important target organ for hypoxia treatment, and hypoxia can induce several diseases in the body. Methods: We performed transcriptome sequencing for the lungs of rats exposed to plateau hypoxia at 0 day and 28 days. Sequencing libraries were constructed, and enrichment analysis of the differentially expressed genes (DEGs) was implemented using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, experimental validation was executed by quantitative real-time PCR (qRT-PCR) and western blot. Results: The results showed that the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) signaling pathway that was involved in immunity may play a crucial function in lung injury caused by plateau hypoxia. And the expressions of NOD1, NOD2, IL-1β, TNF-α, IL-6, and IL-18 were higher at 28 days of exposure to plateau hypoxia than that at 0 day. Similarly, CARD9, MYD88, p38 MAPK, and NF-κB p65, which are related to the NF-κB and MAPK signaling pathways, also demonstrated increased expression at 28 days exposure to plateau hypoxia than at 0 day. Conclusions: Our study suggested that the NFκBp65 and p38 MAPK signaling pathways may be activated in the lungs of rats during plateau hypoxia. Upregulated expression of NFκBp65 and p38 MAPK can promote the transcription of downstream inflammatory factors, thereby aggravating the occurrence and development of lung tissue remodeling. Keywords: Plateau hypoxia, Lung, Inflammatory, Transcriptome sequence, NOD-like receptors
Introduction About 2% of the world’s total population lives in highaltitude areas (generally ≥ 2500 m), and in China alone, areas above 3000 m account for 25% of the country’s land [1]. Moreover, with the continuous development of tourism, the economy, and national defense, increasing numbers of people will enter high-altitude areas to live and work [2]. The plateau is an ecological environment * Correspondence: [email protected] 1 College of Medicine, Qinghai University, Xining 810001, Qinghai Province, China 2 Qinghai Normal University, Xining 810007, Qinghai Province, China
which possesses some special features, such as low oxygen, high radiation, and low pressure [3]. When humans access the plateau environment from the plains, their organs and tissues undergo physiological hypoxia. High altitude actuates the body to decrease partial pressure and oxygen saturation of the arterial blood, eventually leading to tissue hypoxia [4]. On the other hand, hypoxia can cause high-altitude pulmonary edema (HAPE) [5], high-altitude cerebral edema (HACE) [6], polycythemia, and cardiovascular diseases [7]. As the lung is the most sensitive organ to oxygen, hypoxia can cause lung damage. Especially concerning is the risk that acute high-
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attributio
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