دورية أكاديمية
Biglycan evokes autophagy in macrophages via a novel CD44/Toll-like receptor 4 signaling axis in ischemia/reperfusion injury.
| العنوان: | Biglycan evokes autophagy in macrophages via a novel CD44/Toll-like receptor 4 signaling axis in ischemia/reperfusion injury. |
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| المؤلفون: | Poluzzi C; Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany., Nastase MV; Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany; National Institute for Chemical-Pharmaceutical Research and Development, Bucharest, Romania., Zeng-Brouwers J; Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany., Roedig H; Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany., Hsieh LT; Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany., Michaelis JB; Institut für Biochemie II, Klinikum der JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany., Buhl EM; Electron Microscopy Facility, RWTH Aachen University Hospital, Aachen, Germany; Institute of Pathology & Department of Nephrology, RWTH Aachen University Hospital, Aachen, Germany., Rezende F; Institute for Cardiovascular Physiology, JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany., Manavski Y; Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany; German Centre of Cardiovascular Research (DZHK), Rhein-Main, Germany., Bleich A; Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany., Boor P; Institute of Pathology & Department of Nephrology, RWTH Aachen University Hospital, Aachen, Germany., Brandes RP; Institute for Cardiovascular Physiology, JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany., Pfeilschifter J; Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany., Stelzer EHK; Physical Biology/Physikalische Biologie (IZN, FB 15), Buchmann Institute for Molecular Life Sciences (BMLS), Cluster of Excellence Frankfurt - Macromolecular Complexes (CEF-MC), JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany., Münch C; Institut für Biochemie II, Klinikum der JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany., Dikic I; Institute of Biochemistry II, Goethe University Medical School, Frankfurt, Germany., Brandts C; Department of Medicine, Hematology/Oncology, Goethe University, Frankfurt, Germany., Iozzo RV; Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA., Wygrecka M; Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Giessen, Germany., Schaefer L; Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany. Electronic address: Schaefer@med.uni-frankfurt.de. |
| المصدر: | Kidney international [Kidney Int] 2019 Mar; Vol. 95 (3), pp. 540-562. Date of Electronic Publication: 2019 Jan 31. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 0323470 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-1755 (Electronic) Linking ISSN: 00852538 NLM ISO Abbreviation: Kidney Int Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2016- : New York : Elsevier Original Publication: New York, Springer-Verlag. |
| مواضيع طبية MeSH: | Acute Kidney Injury/*immunology , Biglycan/*metabolism , Hyaluronan Receptors/*metabolism , Macrophages/*immunology , Reperfusion Injury/*immunology, Acute Kidney Injury/pathology ; Animals ; Autophagosomes/immunology ; Autophagosomes/metabolism ; Autophagy/immunology ; Biglycan/genetics ; Biglycan/immunology ; Cells, Cultured ; Disease Models, Animal ; Humans ; Hyaluronan Receptors/genetics ; Hyaluronan Receptors/immunology ; Kidney Tubules/blood supply ; Kidney Tubules/immunology ; Kidney Tubules/pathology ; Macrophage Activation ; Mice ; Mice, Knockout ; Primary Cell Culture ; Reperfusion Injury/pathology ; Signal Transduction/genetics ; Signal Transduction/immunology ; Toll-Like Receptor 4/genetics ; Toll-Like Receptor 4/metabolism |
| مستخلص: | Biglycan, a small leucine-rich proteoglycan, acts as a danger signal and is classically thought to promote macrophage recruitment via Toll-like receptors (TLR) 2 and 4. We have recently shown that biglycan signaling through TLR 2/4 and the CD14 co-receptor regulates inflammation, suggesting that TLR co-receptors may determine whether biglycan-TLR signaling is pro- or anti-inflammatory. Here, we sought to identify other co-receptors and characterize their impact on biglycan-TLR signaling. We found a marked increase in the number of autophagic macrophages in mice stably overexpressing soluble biglycan. In vitro, stimulation of murine macrophages with biglycan triggered autophagosome formation and enhanced the flux of autophagy markers. Soluble biglycan also promoted autophagy in human peripheral blood macrophages. Using macrophages from mice lacking TLR2 and/or TLR4, CD14, or CD44, we demonstrated that the pro-autophagy signal required TLR4 interaction with CD44, a receptor involved in adhesion, migration, lymphocyte activation, and angiogenesis. In vivo, transient overexpression of circulating biglycan at the onset of renal ischemia/reperfusion injury (IRI) enhanced M1 macrophage recruitment into the kidneys of Cd44 +/+ and Cd44 -/- mice but not Cd14 -/- mice. The biglycan-CD44 interaction increased M1 autophagy and the number of renal M2 macrophages and reduced tubular damage following IRI. Thus, CD44 is a novel signaling co-receptor for biglycan, an interaction that is required for TLR4-CD44-dependent pro-autophagic activity in macrophages. Interfering with the interaction between biglycan and specific TLR co-receptors could represent a promising therapeutic intervention to curtail kidney inflammation and damage. (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Kidney Int. 2019 Mar;95(3):489-491. (PMID: 30784655) |
| فهرسة مساهمة: | Keywords: DAMP; M2 polarization; Toll-like receptor; inflammation; ischemia/reperfusion injury |
| المشرفين على المادة: | 0 (BGN protein, human) 0 (Bgn protein, mouse) 0 (Biglycan) 0 (CD44 protein, human) 0 (Cd44 protein, mouse) 0 (Hyaluronan Receptors) 0 (Toll-Like Receptor 4) |
| تواريخ الأحداث: | Date Created: 20190205 Date Completed: 20200214 Latest Revision: 20200214 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.kint.2018.10.037 |
| PMID: | 30712922 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1523-1755 |
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| DOI: | 10.1016/j.kint.2018.10.037 |