مورد إلكتروني
Novel mineralocorticoid receptor mechanisms regulate cardiac tissue inflammation in male mice.
| العنوان: | Novel mineralocorticoid receptor mechanisms regulate cardiac tissue inflammation in male mice. |
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| بيانات النشر: | BioScientifica Ltd. (Euro House, 22 Apex Court, Woodlands, Bradley Stoke, Bristol BS32 4JT, United Kingdom) United Kingdom 2020-08-22 |
| تفاصيل مُضافة: | Cole T.J. Dowling J.K. Mansell A. Fuller P.J. Young M.J. Tesch G.H. Ong G.S.Y. Morgan J. |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | MR activation in macrophages is critical for the development of cardiac inflammation and fibrosis. We previously showed that MR activation modifies macrophage pro-inflammatory signalling, changing the cardiac tissue response to injury via both direct gene transcription and JNK/AP-1 second messenger pathways. In contrast, MR-mediated renal electrolyte homeostasis is critically determined by DNA-binding-dependent processes. Hence, ascertaining the relative contribution of MR actions via DNA binding or alternative pathways on macrophage behaviour and cardiac inflammation may provide therapeutic opportunities which separate the cardioprotective effects of MR antagonists from their undesirable renal potassium-conserving effects. We developed new macrophage cell lines either lacking MR or harbouring a mutant MR incapable of DNA binding. Western blot analysis demonstrated that MR DNA binding is required for lipopolysaccharide (LPS), but not phorbol 12-myristate-13-acetate (PMA), induction of the MAPK/pJNK pathway in macrophages. Quantitative RTPCR for pro-inflammatory and pro-fibrotic targets revealed subsets of LPS- and PMA-induced genes that were either enhanced or repressed by the MR via actions that do not always require direct MR-DNA binding. Analysis of the MR target gene and profibrotic factor MMP12 identified promoter elements that are regulated by combined MR/MAPK/JNK signalling. Evaluation of cardiac tissue responses to an 8-day DOC/salt challenge in mice selectively lacking MR DNA-binding in macrophages demonstrated levels of inflammatory markers equivalent to WT, indicating non-DNA binding-dependent MR signalling in macrophages is sufficient for DOC/salt-induced tissue inflammation. Our data demonstrate that the MR regulates a macrophage pro-inflammatory phenotype and cardiac tissue inflammation, partially via pathways that do not require DNA binding.Copyright © 2020 Society for Endocrinology Published by Bioscientifica Ltd. Printed in Great Britain |
| مصطلحات الفهرس: | Western blotting, glucocorticoid receptor/ec [Endogenous Compound], interleukin 10/ec [Endogenous Compound], interleukin 1beta/ec [Endogenous Compound], interleukin 33/ec [Endogenous Compound], interleukin 6/ec [Endogenous Compound], macrophage elastase/ec [Endogenous Compound], mineralocorticoid receptor/ec [Endogenous Compound], prostaglandin synthase/ec [Endogenous Compound], toll like receptor 4/ec [Endogenous Compound], macrophage, mouse, animal cell, animal experiment, animal model, animal tissue, article, bone marrow derived macrophage, carditis/et [Etiology], controlled study, DNA binding, genotype, heart muscle fibrosis/et [Etiology], male, macrophage cell line, nonhuman, priority journal, promoter region, signal transduction, transactivation assay, transcription regulation, Article |
| URL: | Journal of Endocrinology LibKey Link |
| الإتاحة: | Open access content. Open access content Copyright 2020 Elsevier B.V., All rights reserved. |
| أرقام أخرى: | AUSHL oai:repository.monashhealth.org:1/29150 Journal of Endocrinology. 246 (2) (pp 123-134), 2020. Date of Publication: August 2020. 0022-0795 https://repository.monashhealth.org/monashhealthjspui/handle/1/29150Test 32464598 [http://www.ncbi.nlm.nih.gov/pubmed/?term=32464598Test] 2007138273 (Ong, Morgan, Dowling, Mansell, Fuller, Young) Hudson Institute of Medical Research, Clayton, VIC, Australia (Ong, Morgan, Mansell, Fuller, Young) Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, Australia (Ong) Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Murdoch, WA, Australia (Ong) Department of General Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia (Cole) Department of Biochemistry, Monash University, Clayton, VIC, Australia (Tesch) Department of Medicine, Monash University, Clayton, VIC, Australia (Tesch) Department of Nephrology, Monash Medical Centre, Clayton, VIC, Australia (Dowling) Royal College of Surgeons in Ireland, Dublin, Ireland Young M.J.; morag.young@baker.edu.au 1305109134 |
| المصدر المساهم: | MONASH HEALTH LIBRS From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1305109134 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |