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Integration of metabolomics and transcriptomics analyses reveals sphingosine-1-phosphate-mediated S1PR2/PI3K/Akt pathway involved in Talaromyces marneffei infection of macrophages

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机构: [1]Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, China [2]NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China [3]Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, China [4]School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming, China [5]Hubei Provincial Key Laboratory of Occurrence and Intervention of Kidney Diseases, Medical College, Hubei Polytechnic University, Huangshi, China
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关键词: T marneffei Metabolomics Transcriptomics Sphingolipid S1P

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Talaromycosis is a fatal mycosis caused by the thermally dimorphic fungus Talaromyces marneffei (T. marneffei). The pathogenic mechanisms of talaromycosis are still poorly understood. This work combined metabolomics, transcriptomics, and verification experiments in vivo and in vitro to detect metabolic profiles and differentially expressed genes (DEGs) in T. marneffei infected and uninfected macrophages to explore possible pathogenesis and underlying mechanisms. A total of 256 differential metabolites (117 up-regulated and 148 down-regulated) and 1320 DEGs (1286 up-regulated and 34 down-regulated) were identified between the two groups. Integrative metabolomics and transcriptomics analysis showed sphingolipid signaling pathway is the most influential. Verification experiments showed that compared with the control group, the production of sphingosine-1-phosphate (S1P) and the expression of the S1PR1, S1PR2, phosphor-PI3K, and phosphor-Akt genes involved in the sphingolipid signaling pathway have significantly increased in the T. marneffei infection group (p < 0.05). T. marneffei activates the S1PR2/PI3K/Akt pathways in J774A.1 macrophage, regulation of the S1P singling might serve as a promising therapeutic strategy for talaromycosis.Copyright © 2023 Elsevier Ltd. All rights reserved.

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大类 | 3 区 医学
小类 | 3 区 免疫学 3 区 微生物学
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出版当年[2023]版:
Q2 MICROBIOLOGY Q3 IMMUNOLOGY
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Q2 MICROBIOLOGY Q3 IMMUNOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2022版]

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第一作者机构: [1]Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, China
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通讯机构: [1]Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, China [2]NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China [3]Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, China [*1]Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China. [*2]NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
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