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Tracing the failing heart: dual genetic fate mapping for target identification

Signal Transduction and Targeted Therapy 2023年第9期8卷 3880-3882页

作者： Yaw Asare Christian Stoppe jürgen bernhagen Institute for Stroke and Dementia Research(ISD) Klinikum der Universität München(KUM)Ludwig-Maximilian-University(LMU)81377 MunichGermany Department of Anesthesiology Intensive CareEmergency and Pain MedicineUniversity Hospital Würzburg97080 WürzburgGermany Department of Cardiac Anesthesiology and Intensive Care Medicine German Heart Center CharitéBerlin13353 BerlinGermany Munich Cluster for Systems Neurology 81377 MunichGermany Munich Heart Alliance 80802 MunichGermany

In a recent study published in Nature Genetics,1 Han and colleagues employed a dual genetic lineage tracing approach in combination with a model of heart failure(HF)to identify a key sub-population of endocardium-derived fibroblasts,which gives rise to excessive myofibroblast formation in a Wnt pathway-mediated manner and contributes to cardiac fibrosis.1 The identified fibroblast sub-population and Wnt signaling pathway could be novel targets for the therapy of *** in risk management and cardiovascular inter-vention have significantly reduced age-specific cardiovascular disease-related *** contrast,the rate of HF-related hospitalisations has increased over the past decades and HF is a disease with highest social and economic cost in industrialized *** is defined as impairment of the heart’s blood pumping function and its severity is assessed based on ejection *** often occurs after myocardial infarction(MI),with infarct size and quality of ventricular remodeling after MI influencing ventricular *** of HF also include hypertension,atrial fibrillation,and cardiomyopathies(Fig.1).Especially elderly patients with recurrent MI and comorbidities are increasingly presenting with signs of HF.

关键词： cardiovascular ventricular mortality

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IKKβ binds NLRP3 providing a shortcut to inflammasome activation for rapid immune responses

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Signal Transduction and Targeted Therapy 2022年第11期7卷 4022-4024页

作者： Yaw Asare Margarita Shnipova LukaŽivković Christina Schlegl Federica Tosato Arailym Aronova Markus Brandhofer Laura Strohm Nathalie Beaufort Rainer Malik Christian Weber jürgen bernhagen Martin Dichgans Institute for Stroke and Dementia Research(ISD) University HospitalLudwig-Maximilians-University(LMU)MunichGermany Munich Cluster for Systems Neurology(SyNergy) MunichGermany Institute for Cardiovascular Prevention(IPEK) LMUMunichGermany

Dear Editor,A rapid immune response to signals released from pathogens and injuries is critical for maintaining tissue integrity and restoring *** response is largely mediated by the concerted action of pattern recognition receptors(PRRs).Such cooperativity has been described for Toll-like receptors(TLRs)and NACHT,LRR,and pyrin domain-containing protein 3(NLRP3),but the underlying molecular mechanisms remain incompletely *** are multi-protein complexes defined by a cytosolic innate immune sensor,usually a PRR,which recruits the adaptor molecule apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC)to activate the effector caspase-1 leading to the release of matured IL-1βand *** caspase-1 further cleaves gasdermin D(GSDMD)allowing the N-terminal domain of GSDMD(GSDMD-N)to form pores in the plasma membrane,thus facilitating the release of matured IL-1βand ***-forming GSDMD-N further induces pyroptosis,an inflammatory form of cell death.

关键词： NLRP3 release activation

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Modulating effects of acyl-CoA synthetase 5-derived mitochondrial Wnt2B palmitoylation on intestinal Wnt activity

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World journal of Gastroenterology 2014年第40期20卷 14855-14864页

作者： Christina Klaus Ursula Schneider Christian Hedberg Anke K Schütz jürgen bernhagen Herbert Waldmann Nikolaus Gassler Elke Kaemmerer Institute of Pathology RWTH Aachen University 52074 Aachen Germany Department of Chemical Biology Max Planck Institute of Molecular Physiology 44227 Dortmund Germany Department of Biochemistry and Molecular Cell Biology RWTH Aachen University 52074 Aachen Germany Department of Pediatrics RWTH Aachen University 52074 Aachen Germany

AIM:To investigate the role of acyl-CoA synthetase 5(ACSL5)activity in Wnt signaling in intestinal surface ***:Several cell lines were used to investigate the ACSL5-dependent expression and synthesis of Wnt2B,a mitochondrially expressed protein of the Wnt signaling *** activity was functionally assessed with a luciferase reporter ***5-related biochemical Wnt2B modifications were investigatedwith a modified acyl-exchange *** findings from the cell culture models were verified using an Apcmin/+mouse model as well as normal and neoplastic diseased human intestinal ***:In the presence of ACSL5,Wnt2B was unable to translocate into the nucleus and was enriched in mitochondria,which was paralleled by a significant decrease in Wnt ***5-dependent S-palmitoylation of Wnt2B was identified as a molecular reason for mitochondrial Wnt2B *** cell culture systems,a strong relation of ACSL5 expression,Wnt2B palmitoylation,and degree of malignancy were *** normal mucosa,the association of ACSL5 and Wnt2B was seen,but in intestinal neoplasias the mechanism was only rudimentarily ***:ACSL5 mediates antiproliferative activities via Wnt2B palmitoylation with diminished Wnt *** molecular pathway is probably relevant for intestinal homeostasis,overwhelmed by other pathways in carcinogenesis.

关键词： Acyl-CoA synthetases Wnt signaling Palmitoylation

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