Stressed hepatocyte sustains alcohol-associated hepatitis progression by producing leukocyte cell-derived chemotaxin 2 DOI
Honghai Xu, Zihao Wu,

Jiangfeng Qin

et al.

Gut, Journal Year: 2025, Volume and Issue: unknown, P. gutjnl - 334318

Published: March 26, 2025

Background Neutrophil infiltration and hepatocyte damage are indispensable hallmarks in alcohol-associated hepatitis (AH), yet the underlying crosstalk between neutrophils hepatocytes its role AH pathogenesis remain unclear. Objective We investigate regulatory of leucocyte cell-derived chemotaxin 2 (LECT2) hepatocyte–neutrophil interaction impact on progression. Design used bulk single-cell RNA sequencing to identify hepatocyte-secreted factors targeting neutrophils. analysed serum liver samples from patients employed genetically modified mice alongside vitro studies. Results RNA-sequencing analysis identified several neutrophil chemokines that elevated patients, including LECT2 whose remains largely unknown. exhibited increased levels hepatocytes, positively correlating with severity AH. Ethanol-fed also LECT2, which was abolished by inhibiting endoplasmic reticulum stress. Functional studies revealed ethanol-induced injury ameliorated Lect2 -deficient but exacerbated hepatic overexpression . Furthermore, promoting reactive oxygen species (ROS) through prohibitin (PHB2), a membrane protein. By directly binding PHB2, disrupts stable structure PHB1/PHB2 heterodimerisation, consequently leading PHB2 degradation, ROS accumulation, activation extracellular trap formation. Moreover, therapeutic intervention via shRNA injury. Conclusion Our novel vicious cycle LECT2–PHB2 interaction, presenting promising mitigate patients.

Language: Английский

Stressed hepatocyte sustains alcohol-associated hepatitis progression by producing leukocyte cell-derived chemotaxin 2 DOI
Honghai Xu, Zihao Wu,

Jiangfeng Qin

et al.

Gut, Journal Year: 2025, Volume and Issue: unknown, P. gutjnl - 334318

Published: March 26, 2025

Background Neutrophil infiltration and hepatocyte damage are indispensable hallmarks in alcohol-associated hepatitis (AH), yet the underlying crosstalk between neutrophils hepatocytes its role AH pathogenesis remain unclear. Objective We investigate regulatory of leucocyte cell-derived chemotaxin 2 (LECT2) hepatocyte–neutrophil interaction impact on progression. Design used bulk single-cell RNA sequencing to identify hepatocyte-secreted factors targeting neutrophils. analysed serum liver samples from patients employed genetically modified mice alongside vitro studies. Results RNA-sequencing analysis identified several neutrophil chemokines that elevated patients, including LECT2 whose remains largely unknown. exhibited increased levels hepatocytes, positively correlating with severity AH. Ethanol-fed also LECT2, which was abolished by inhibiting endoplasmic reticulum stress. Functional studies revealed ethanol-induced injury ameliorated Lect2 -deficient but exacerbated hepatic overexpression . Furthermore, promoting reactive oxygen species (ROS) through prohibitin (PHB2), a membrane protein. By directly binding PHB2, disrupts stable structure PHB1/PHB2 heterodimerisation, consequently leading PHB2 degradation, ROS accumulation, activation extracellular trap formation. Moreover, therapeutic intervention via shRNA injury. Conclusion Our novel vicious cycle LECT2–PHB2 interaction, presenting promising mitigate patients.

Language: Английский

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