The role of forkhead box M1-methionine adenosyltransferase 2 A/2B axis in liver inflammation and fibrosis.

Autor: Yang B; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA.; Department of Geriatric Endocrinology and Metabolism, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention, Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China., Lu L; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA.; Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China., Xiong T; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA.; Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan, 410015, China., Fan W; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA., Wang J; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA., Barbier-Torres L; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA., Chhimwal J; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA., Sinha S; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA., Tsuchiya T; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA., Mavila N; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA., Tomasi ML; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA., Cao D; Department of Biomedical Sciences, CSMC LA, Los Angeles, CA, 90048, USA., Zhang J; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA.; Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Peng H; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA., Mato JM; CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology, Park of Bizkaia, 48120, Derio, Bizkaia, Spain., Liu T; Department of Gastroenterology, Xiangya Hospital, Key Laboratory of Cancer proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China., Yang X; Department of Geriatric Endocrinology and Metabolism, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention, Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China., Kalinichenko VV; Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, 85004, USA.; Division of Neonatology, Phoenix Children's Hospital, Phoenix, AZ, 85016, USA., Ramani K; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA., Han J; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA.; Department of Society and Genetics, UCLA LA, Los Angeles, CA, 92620, USA., Seki E; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA., Yang H; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA. Heping.yang@cshs.org., Lu SC; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, LA, Los Angeles, CA, 90048, USA. shelly.lu@cshs.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Sep 27; Vol. 15 (1), pp. 8388. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1038/s41467-024-52527-8
Abstrakt: Methionine adenosyltransferase 2 A (MAT2A) and MAT2B are essential for hepatic stellate cells (HSCs) activation. Forkhead box M1 (FOXM1) transgenic mice develop liver inflammation and fibrosis. Here we examine if they crosstalk in male mice. We found FOXM1/MAT2A/2B are upregulated after bile duct ligation (BDL) and carbon tetrachloride (CCl 4 ) treatment in hepatocytes, HSCs and Kupffer cells (KCs). FDI-6, a FOXM1 inhibitor, attenuates the development and reverses the progression of CCl 4 -induced fibrosis while lowering the expression of FOXM1/MAT2A/2B, which exert reciprocal positive regulation on each other transcriptionally. Knocking down any of them lowers HSCs and KCs activation. Deletion of FOXM1 in hepatocytes, HSCs, and KCs protects from BDL-mediated inflammation and fibrosis comparably. Interestingly, HSCs from Foxm1 Hep-/- , hepatocytes from Foxm1 HSC-/- , and HSCs and hepatocytes from Foxm1 KC-/- have lower FOXM1/MAT2A/2B after BDL. This may be partly due to transfer of extracellular vesicles between different cell types. Altogether, FOXM1/MAT2A/MAT2B axis drives liver inflammation and fibrosis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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