气候变化领域集成服务门户(CCPortal): JNK signaling prevents biliary cyst formation through a CASPASE-8

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DOI	10.1073/pnas.2007194118
	JNK signaling prevents biliary cyst formation through a CASPASE-8–dependent function of RIPK1 during aging
	Müller K.; Honcharova-Biletska H.; Koppe C.; Egger M.; Chan L.K.; Schneider A.T.; Küsgens L.; Böhm F.; Boege Y.; Healy M.E.; Schmitt J.; Comtesse S.; Castoldi M.; Preisinger C.; Szydlowska M.; Focaccia E.; Gaisa N.T.; Loosen S.H.; Jörs S.; Tacke F.; Roderburg C.; Keitel V.; Bode J.G.; Boor P.; Davis R.J.; Longerich T.; Geisler F.; Heikenwalder M.; Weber A.; Vucur M.; Luedde T.
发表日期	2021
ISSN	00278424
卷号	118 期号:12
英文摘要	The c-Jun N-terminal kinase (JNK) signaling pathway mediates adaptation to stress signals and has been associated with cell death, cell proliferation, and malignant transformation in the liver. However, up to now, its function was experimentally studied mainly in young mice. By generating mice with combined conditional ablation of Jnk1 and Jnk2 in liver parenchymal cells (LPCs) (JNK1/2LPC-KO mice; KO, knockout), we unraveled a function of the JNK pathway in the regulation of liver homeostasis during aging. Aging JNK1/2LPC-KO mice spontaneously developed large biliary cysts that originated from the biliary cell compartment. Mechanistically, we could show that cyst formation in livers of JNK1/2LPC-KO mice was dependent on receptor-interacting protein kinase 1 (RIPK1), a known regulator of cell survival, apoptosis, and necroptosis. In line with this, we showed that RIPK1 was overexpressed in the human cyst epithelium of a subset of patients with polycystic liver disease. Collectively, these data reveal a functional interaction between JNK signaling and RIPK1 in age-related progressive cyst development. Thus, they provide a functional linkage between stress adaptation and programmed cell death (PCD) in the maintenance of liver homeostasis during aging. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cholangiocytes \| liver cysts \| liver \| programmed cell death \| MK2
语种	英语
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/180171
作者单位	Division of Biliary and Gastrointestinal Oncology, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, 52074, Germany; Department of Pathology and Molecular Pathology, University of Zurich, University Hospital Zurich, Zurich, 8091, Switzerland; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University, Duesseldorf, 40225, Germany; Proteomics Core Facility, Interdisciplinary Center for Clinical Research, University Hospital RWTH Aachen, Aachen, 52074, Germany; Division of Chronic Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, 69120, Germany; Institute of Pathology, University Hospital RWTH Aachen, Aachen, 52074, Germany; Internal Medicine II, Klinikum rechts der Isar, Technical University Munich, Munich, 81675, Germany; Department of Hepatology and Gastroenterology, Charité University Medical Center Berlin, Berlin, 10117, Germany; ...
推荐引用方式 GB/T 7714	Müller K.,Honcharova-Biletska H.,Koppe C.,等. JNK signaling prevents biliary cyst formation through a CASPASE-8–dependent function of RIPK1 during aging[J],2021,118(12).
APA	Müller K..,Honcharova-Biletska H..,Koppe C..,Egger M..,Chan L.K..,...&Luedde T..(2021).JNK signaling prevents biliary cyst formation through a CASPASE-8–dependent function of RIPK1 during aging.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	Müller K.,et al."JNK signaling prevents biliary cyst formation through a CASPASE-8–dependent function of RIPK1 during aging".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).