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from: tainan
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from: taoyuan
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from: Kaohsiung
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from: hongkong
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from: yunlin
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from: Kaohsiung
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from: london
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from: taizhong
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Dr. Song
from: Kaohsiung
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| 2024-01-09 12:26:58 | onclick： | Scientists Reveal New Target for ABCG2 Antimicrobial Therapy |
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Li Xin's research team published a paper online in the journal Cell Metabolism, revealing that the transporter ABCG2 inhibits antibacterial natural immunity of macrophages through exocytoconic acid.
Itaconic acid is a cellular metabolite with immunomodulatory functions, and current research has found that it is produced mainly in inflammatory activated macrophages by the metabolic enzyme IRG1 located in mitochondria.However, the mechanism of concentration regulation of itaconic acid in macrophages and its biological significance are unclear.Transporter ABCG2 belongs to the ABC (ATP-binding Cassette) transporter family. It is widely expressed in intestines, liver, placenta and blood-brain barrier, and can actively pump metabolites and small molecule drugs out of the cell.Based on this characteristic, numerous studies have reported that ABCG2 is associated with resistance to tumor chemotherapy.
In this study, the researchers constructed a library of slow virus gRNAs targeting membrane-localizing protein coding genes, and selected ABCG2 gene as the extracellular transport protein in inflammatory macrophages by using itaconic acid probe BioITA as output signal.Subsequently, ABCG2 was confirmed by mass spectrometry, flow cytometry and recombinant liposome analysis to be an extracellular transport protein of itaconic acid, and its transport activity depended on hydrolysis of ATP.In order to further investigate the physiological function of ABCG2-mediated extracellular transport of itaconic acid, the researchers constructed a mouse model of Salmonella typhoid infection.In addition, the mechanism study showed that ABCG2-mediated extracellular transport of itaconic acid could lower the concentration of itaconic acid and limit the activation of itaconic acid-mediated TFEB.
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