KMID : 1034820220180030419
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Molecular & Cellular Toxicology 2022 Volume.18 No. 3 p.419 ~ p.429
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LRG1 expression reduced inflammation of sepsis-renal injury via activation of NLRP3 inflammasome by HIF-1 alpha
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Du Wenjing
Sang Yiquan Bai Yun-Huan
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Abstract
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Background: Sepsis is a commonly seen severe case in clinical practice and the main cause of health loss worldwide.
Objective: We investigated the biological function of LRG1 and its underlying molecular mechanisms in sepsis-renal injury. Mice of sepsis model group were subjected to cecal ligation and puncture (CLP) surgery after anesthetization. THP-1 cell was induced by LPS for vitro model.
Results: The mRNA and protein levels of LRG1 in renal tissue of sepsis model were reduced. LRG1 could reduce the inflammation reaction in model of sepsis-renal injury. In addition, LRG1 up-regulation reduced inflammation reaction and ROS production levels in vitro model via the activation of HIF-1¥á and suppression of NLRP3 inflammasome. Knockout of LRG1 increased inflammation reaction and ROS production levels in vitro model via the inactivation of HIF-1¥á and induction of NLRP3 inflammasome. Furthermore, the inhibition of HIF-1¥á reduced the effects of LRG1 on NLRP3 inflammasome in vitro model.
Conclusions: The present study suggests that LRG1 expression reduced inflammation of sepsis-renal injury via activation of NLRP3 inflammasome by HIF-1¥á, thereby may be a promising therapeutic target of sepsis-renal injury.
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KEYWORD
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LRG1, NLRP3, HIF-1¥á, Sepsis, Renal injury
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