气候变化领域集成服务门户(CCPortal): Up-regulation of miR-34b/c by JNK and FOXO3 protects from liver fibrosis

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DOI	10.1073/pnas.2025242118
	Up-regulation of miR-34b/c by JNK and FOXO3 protects from liver fibrosis
	Piccolo P.; Ferriero R.; Barbato A.; Attanasio S.; Monti M.; Perna C.; Borel F.; Annunziata P.; Carissimo A.; De Cegli R.; Quagliata L.; Terracciano L.M.; Housset C.; Teckman J.H.; Mueller C.; Brunetti-Pierri N.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	α1-Antitrypsin (AAT) deficiency is a common genetic disease presenting with lung and liver diseases. AAT deficiency results from pathogenic variants in the SERPINA1 gene encoding AAT and the common mutant Z allele of SERPINA1 encodes for Z α1-antitrypsin (ATZ), a protein forming hepatotoxic polymers retained in the endoplasmic reticulum of hepatocytes. PiZ mice express the human ATZ and are a valuable model to investigate the human liver disease of AAT deficiency. In this study, we investigated differential expression of microRNAs (miRNAs) between PiZ and control mice and found that miR-34b/c was up-regulated and its levels correlated with intrahepatic ATZ. Furthermore, in PiZ mouse livers, we found that Forkhead Box O3 (FOXO3) driving microRNA-34b/c (miR‐34b/c) expression was activated and miR-34b/c expression was dependent upon c-Jun N-terminal kinase (JNK) phosphorylation on Ser574. Deletion of miR-34b/c in PiZ mice resulted in early development of liver fibrosis and increased signaling of platelet-derived growth factor (PDGF), a target of miR-34b/c. Activation of FOXO3 and increased miR-34c were confirmed in livers of humans with AAT deficiency. In addition, JNK-activated FOXO3 and miR-34b/c up-regulation were detected in several mouse models of liver fibrosis. This study reveals a pathway involved in liver fibrosis and potentially implicated in both genetic and acquired causes of hepatic fibrosis. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	FOXO3; JNK; Liver fibrosis; Mir-34b/c; α1 antitrypsin deficiency
语种	英语
scopus关键词	microRNA; microRNA 34b; microRNA 34c; platelet derived growth factor; stress activated protein kinase; transcription factor FKHRL1; unclassified drug; alpha 1 antitrypsin deficiency; animal experiment; animal model; animal tissue; Article; controlled study; gene deletion; gene expression; genetic correlation; liver fibrosis; male; mouse; nonhuman; priority journal; protein phosphorylation; signal transduction; upregulation
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180384
作者单位	Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, 80078, Italy; Department of Translational Medicine, Federico II University, Naples, 80131, Italy; Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655, United States; Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01655, United States; Molecular Pathology Division, Institute of Pathology, University Hospital of Basel, University of Basel, Basel, 4003, Switzerland; Centre de Recherche Saint-Antoine, Sorbonne Université, INSERM, Paris, 75012, France; Department of Hepatology, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, 75012, France; Cardinal Glennon Children’s Medical Center, St. Louis University School of Medicine, St. Louis, MO 63104, United States
推荐引用方式 GB/T 7714	Piccolo P.,Ferriero R.,Barbato A.,et al. Up-regulation of miR-34b/c by JNK and FOXO3 protects from liver fibrosis[J],2021,118(10).
APA	Piccolo P..,Ferriero R..,Barbato A..,Attanasio S..,Monti M..,...&Brunetti-Pierri N..(2021).Up-regulation of miR-34b/c by JNK and FOXO3 protects from liver fibrosis.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Piccolo P.,et al."Up-regulation of miR-34b/c by JNK and FOXO3 protects from liver fibrosis".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).