The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages
Open accessAbstract
Biglycan, a small leucine-rich proteoglycan, is a ubiquitous ECM component; however, its biological role has not been elucidated in detail. Here we show that biglycan acts in macrophages as an endogenous ligand of TLR4 and TLR2, which mediate innate immunity, leading to rapid activation of p38, ERK, and NF-kappaB and thereby stimulating the expression of TNF-alpha and macrophage inflammatory protein-2 (MIP-2). In agreement, the stimulatory effects of biglycan are significantly reduced in TLR4-mutant (TLR4-M), TLR2-/-, and myeloid differentiation factor 88-/- (MyD88-/-) macrophages and completely abolished in TLR2-/-/TLR4-M macrophages. Biglycan-null mice have a considerable survival benefit in LPS- or zymosan-induced sepsis due to lower levels of circulating TNF-alpha and reduced infiltration of mononuclear cells in the lung, which cause less end-organ damage. Importantly, when stimulated by LPS-induced proinflammatory factors, macrophages themselves are able to synthesize biglycan. Thus, biglycan, upon release from the ECM or from macrophages, can boost inflammation by signaling through TLR4 and TLR2, thereby enhancing the synthesis of TNF-alpha and MIP-2. Our results provide evidence for what is, to our knowledge, a novel role of the matrix component biglycan as a signaling molecule and a crucial proinflammatory factor. These findings are potentially relevant for the development of new strategies in the treatment of sepsis.
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ECM-bioscaffold degradation products function as DAMPs that ligate pattern-recognition and scavenger receptors on dendritic cells and macrophages; in some contexts they also signal via integrins.
“ECM-bioscaffold degradation products function as damage-associated molecular patterns (DAMPs) that ligate pattern-recognition and scavenger receptors on dendritic cells and macrophages; in some contexts, they also signal via integrins [2,26,28,29].”
From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [29]
The Discussion reports that ECM-derived biglycan can be liberated during inflammation and signal through TLR4 and TLR2 in macrophages; the Introduction also reports biglycan binding to a macrophage scavenger receptor. The Discussion mentions hyaluronan-derived oligosaccharides activating TLR4, but the paper does not establish the claim for ECM-bioscaffold degradation products generally or support the integrin-signaling clause. It specifies that intact biglycan, rather than its isolated glycosaminoglycan chains, delivered the macrophage proinflammatory signal. Page numbers are not available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThere is evidence for a role of TLR2 and/or TLR4 in the induction of cytokine and chemokine production in response to extracellular matrix components, including hyaluronan fragments or soluble proteoglycan components, in vitro and in vivo.
“For example, there is evidence for a role of TLR2 and/or TLR4 in the induction of cytokine and chemokine production in response to extracellular matrix components, including hyaluronan fragments or soluble proteoglycan components, in vitro and in vivo31–34.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [33]
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Cites
Chen, Y., Wang, L., Kang, Q., Zhang, X., Yu, G., Wan, X., Wang, J., & Zhu, K. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000477308 · Cited by 10,730 · see citing works
Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394 · see citing works
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in <i>Tlr4</i> Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631 · see citing works
A human homologue of the Drosophila Toll protein signals activation of adaptive immunity
Medzhitov, R., Preston-Hurlburt, P., & Janeway, C. A. J. (1997) · Nature · doi:10.1038/41131 · Cited by 6,137 · see citing works
Toll-like receptors in innate immunity
Takeda, K. (2004) · International Immunology · doi:10.1093/intimm/dxh186 · Cited by 3,328 · see citing works
The immunopathogenesis of sepsis
Cohen, J. (2002) · Nature · doi:10.1038/nature01326 · Cited by 2,742 · see citing works
Points of control in inflammation
Nathan, C. (2002) · Nature · doi:10.1038/nature01320 · Cited by 2,738 · see citing works
Medzhitov, R. M., & Janeway, C. A. (2000) · New England Journal of Medicine · doi:10.1056/nejm200008033430506 · Cited by 1,827 · see citing works
Endotoxin-tolerant Mice Have Mutations in Toll-like Receptor 4 ( Tlr4 )
Qureshi, S. T., Larivière, L., Leveque, G., Clermont, S., Moore, K. J., Gros, P., & Malo, D. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.4.615 · Cited by 1,525 · see citing works
Inferences, questions and possibilities in Toll-like receptor signalling
Beutler, B. (2004) · Nature · doi:10.1038/nature02761 · Cited by 1,458 · see citing works
Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4
Termeer, C., Benedix, F., Sleeman, J., Fieber, C., Voith, U., Ahrens, T., Miyake, K., Freudenberg, M., Galanos, C., & Simon, J. C. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20001858 · Cited by 1,378 · see citing works
The Extra Domain A of Fibronectin Activates Toll-like Receptor 4
Okamura, Y., Watari, M., Jerud, E. S., Young, D. W., Ishizaka, S. T., Rose, J., Chow, J. C., & Strauss, J. F. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100099200 · Cited by 1,217 · see citing works
Hildebrand, A., Romarı́s, M., Rasmussen, L. M., Heinegård, D. K., Twardzik, D. R., Border, W. A., & Ruoslahti, E. I. (1994) · Biochemical Journal · doi:10.1042/bj3020527 · Cited by 995 · see citing works
Leucine-rich repeats and pathogen recognition in Toll-like receptors
Bell, J. K., Mullen, G. E. D., Leifer, C. A., Mazzoni, A., Davies, D. R., & Segal, D. M. (2003) · Trends in Immunology · doi:10.1016/s1471-4906(03)00242-4 · Cited by 766 · see citing works
The Biology of the Small Leucine-rich Proteoglycans
Iozzo, R. V. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.27.18843 · Cited by 646 · see citing works
Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice
Xu, T., Bianco, P., Fisher, L. W., Longenecker, G., Smith, E. A., Goldstein, S. A., Bonadio, J. F., Boskey, A. L., Heegaard, A., Sommer, B., et al. (1998) · Nature Genetics · doi:10.1038/1746 · Cited by 612 · see citing works
Self-citationMiethke, T., Wahl, C., Heeg, K., Echtenacher, B., Krammer, P. H., & Wagner, H. (1992) · The Journal of experimental medicine · doi:10.1084/jem.175.1.91 · Cited by 574 · see citing works
Vimentin is secreted by activated macrophages
Mor-Vaknin, N., Punturieri, A., Sitwala, K., & Markovitz, D. M. (2003) · Nature Cell Biology · doi:10.1038/ncb898 · Cited by 522 · see citing works
Microbial adherence to and invasion through proteoglycans
Rostand, K. S., & Esko, J. D. (1997) · Infection and Immunity · doi:10.1128/iai.65.1.1-8.1997 · Cited by 491 · see citing works
Dermatan sulfate: new functions from an old glycosaminoglycan
Trowbridge, J. M., & Gallo, R. L. (2002) · Glycobiology · doi:10.1093/glycob/cwf066 · Cited by 459 · see citing works
Antisera and cDNA probes to human and certain animal model bone matrix noncollagenous proteins
Fisher, L. W., Stubbs, J. T., & Young, M. F. (1995) · Acta Orthopaedica Scandinavica · doi:10.3109/17453679509157649 · Cited by 446 · see citing works
Self-citationChieppa, M., Bianchi, G., Doni, A., Prete, A. D., Sironi, M., Laškarin, G., Monti, P., Piemonti, L., Biondi, A., Mantovani, A., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.9.4552 · Cited by 368 · see citing works
Ameye, L., Aria, D., Jepsen, K. J., et al. (2002) · The FASEB Journal · doi:10.1096/fj.01-0848com · Cited by 350 · see citing works
Anti-tumor necrosis factor therapy in sepsis: Update on clinical trials and lessons learned
Reinhart, K., & Karzai, W. (2001) · Critical Care Medicine · doi:10.1097/00003246-200107001-00037 · Cited by 289 · see citing works
The role of p38 mitogen-activated protein kinase in IL-1 beta transcription.
Baldassare, J. J., Bi, Y., & Bellone, C. J. (1999) · PubMed · Cited by 242 · see citing works
Toll, A New Piece in the Puzzle of Innate Immunity
Wright, S. D. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.4.605 · Cited by 235 · see citing works
Westergren‐Thorsson, G., Hernnäs, J., Särnstrand, B., Oldberg, Å., Heinegård, D. K., & Malmström, A. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116631 · Cited by 232 · see citing works
The Role of p38 Mitogen-Activated Protein Kinase in IL-1β Transcription
Baldassare, J. J., Bi, Y., & Bellone, C. J. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.9.5367 · Cited by 224 · see citing works
Hippenstiel, S., Soeth, S., Kellas, B., Fuhrmann, O., Seybold, J., Krüll, M., von Eichel‐Streiber, C., Goebeler, M., Ludwig, S., & Suttorp, N. (2000) · Blood · doi:10.1182/blood.v95.10.3044 · Cited by 175 · see citing works
The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens
He, Y.-W., Li, H., Zhang, J., Hsu, C.-L., Lin, E., Zhang, N., Guo, J., Forbush, K. A., & Bevan, M. J. (2004) · Nature Immunology · doi:10.1038/ni1021 · Cited by 171 · see citing works
γδ T cell–induced hyaluronan production by epithelial cells regulates inflammation
Jameson, J., Cauvi, G., Sharp, L. L., Witherden, D. A., & Havran, W. L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042057 · Cited by 162 · see citing works
Carbohydrate-mediated recognition systems in innate immunity
Feizi, T. (2000) · Immunological Reviews · doi:10.1034/j.1600-065x.2000.917310.x · Cited by 161 · see citing works
Schaefer, L., Mačáková, K., Raslik, I., Micegova, M., Gröne, H., Schönherr, E., Robenek, H., Echtermeyer, F. G., Grässel, S., Brückner, P., et al. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64937-1 · Cited by 160 · see citing works
Self-citationToll-like receptor signal transduction and the tailoring of innate immunity: a role for Mal?
O'Neill, L. A. J. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02222-6 · Cited by 154 · see citing works
Guo, R., & Ward, P. A. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00823-7 · Cited by 150 · see citing works
Reimann, T., Büscher, D., Hipskind, R. A., Krautwald, S., Lohmann-Matthes, M.-L., & Baccarini, M. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.153.12.5740 · Cited by 146 · see citing works
Biglycan is overexpressed in pancreatic cancer and induces G1-arrest in pancreatic cancer cell lines
Weber, C. K., Sommer, G., Michl, P., et al. (2001) · Gastroenterology · doi:10.1053/gast.2001.27222 · Cited by 141 · see citing works
Schaefer, L., Raslik, I., Gröne, H., Schönherr, E., Mačáková, K., Ugorcakova, J., Budny, S., Schaefer, R. M., & Kresse, H. (2001) · The FASEB Journal · doi:10.1096/fj.00-0493fje · Cited by 138 · see citing works
Self-citationTumour necrosis factor‐α interacts with biglycan and decorin
Tufvesson, E., & Westergren‐Thorsson, G. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)03439-7 · Cited by 119 · see citing works
Alon, R., Cahalon, L., Hershkoviz, R., Elbaz, D., Reizis, B., Wallach, D., Akiyama, S. K., Yamada, K. M., & Lider, O. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.152.3.1304 · Cited by 116 · see citing works
Santiago-Garcı́a, J., Kodama, T., & Pitas, R. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208358200 · Cited by 100 · see citing works
Biglycan is a new extracellular component of the Chordin–BMP4 signaling pathway
Moreno, M., Muñoz, R., Aroca, F., Labarca, M., Brandan, E., & Larraı́n, J. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600615 · Cited by 99 · see citing works
Tufvesson, E., & Westergren‐Thorsson, G. (2003) · Journal of Cell Science · doi:10.1242/jcs.00808 · Cited by 91 · see citing works
Transcriptional Regulation of the Human Biglycan Gene
Ungefroren, H., & Krull, N. B. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.26.15787 · Cited by 75 · see citing works
Regulation of ?V?3 and ?V?5 integrins by dexamethasone in normal human osteoblastic cells
Cheng, S., Lai, C.-F., Fausto, A., Chellaiah, M. A., Feng, X., McHugh, K. P., Teitelbaum, S. L., Civitelli, R., Hruska, K. A., Ross, F. P., et al. (2000) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(20000501)77:2 · Cited by 71 · see citing works
Decorin Reverses the Repressive Effect of Autocrine-Produced TGF-β on Mouse Macrophage Activation
Comalada, M., Cardó, M., Xaus, J., Valledor, A. F., Lloberas, J., Ventura, F., & Celada, A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.9.4450 · Cited by 68 · see citing works
Biglycan, a Nitric Oxide-regulated Gene, Affects Adhesion, Growth, and Survival of Mesangial Cells
Schaefer, L., Beck, K., Raslik, I., Walpen, S., Mihálik, D., Micegova, M., Mačáková, K., Schönherr, E., Seidler, D. G., Varga, G., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210574200 · Cited by 66 · see citing works
Self-citationAlterations in Large and Small Proteoglycans in Bleomycin-Induced Pulmonary Fibrosis in Rats
Venkatesan, N., Ebihara, T., Roughley, P. J., et al. (2000) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.161.6.9909098 · Cited by 66 · see citing works
Decorin, biglycan and their endocytosis receptor in rat renal cortex
Schaefer, L., Hausser, H., Altenburger, M., et al. (1998) · Kidney International · doi:10.1046/j.1523-1755.1998.00149.x · Cited by 64 · see citing works
Self-citationEndocytosis of different members of the small chondroitin/dermatan sulfate proteoglycan family.
Hausser, H., Ober, B. T., Quentin-Hoffmann, E., et al. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49947-x · Cited by 60 · see citing works
Self-citationSchaefer, L., Mihálik, D., Bábelová, A., et al. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63305-6 · Cited by 58 · see citing works
Self-citationGröne, H., Cohen, C. D., Diaeresis]ne, E. G., Schmidt, C. S., Kretzler, M., Diaeresis]ndorff, D. S., & Nelson, P. J. (2002) · Journal of the American Society of Nephrology · doi:10.1681/asn.v134957 · Cited by 57 · see citing works
Self-citationWalpen, S., Beck, K., Schaefer, L., et al. (2001) · The FASEB Journal · doi:10.1096/fj.00-0518fje · Cited by 54 · see citing works
Self-citationAdenoviral Delivery of Human and Viral IL-10 in Murine Sepsis
Minter, R. M., Ferry, M. A., Murday, M., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.2.1053 · Cited by 40 · see citing works
Tumour necrosis factor-alpha interacts with laminin and functions as a pro-adhesive cytokine.
Hershkoviz, R., Goldkorn, I., & Lider, O. (1995) · PubMed · Cited by 39 · see citing works
Alimohamad, H., Habijanac, T. M., Larjava, H., et al. (2004) · Journal of Periodontal Research · doi:10.1111/j.1600-0765.2004.00776.x · Cited by 36 · see citing works
Different Usage of the Glycosaminoglycan Attachment Sites of Biglycan
Kresse, H., Seidler, D. G., Müller, M., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009321200 · Cited by 29 · see citing works
Haemopoietic biglycan produced by brain cells stimulates growth of microglial cells
Kikuchi, A., Tomoyasu, H., Kido, I., Takahashi, K., Tanaka, A., Nonaka, I., Iwakami, N., & Kamo, I. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00258-1 · Cited by 27 · see citing works
Sime, P. J., Särnstrand, B., Xing, Z., et al. (1997) · CHEST Journal · doi:10.1378/chest.111.6_supplement.137s · Cited by 17 · see citing works
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Sorted by citations
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051 · see citing works
Extracellular matrix structure
Theocharis, A. D., Skandalis, S. S., Gialeli, C., & Karamanos, N. K. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.11.001 · Cited by 2,598 · see citing works
Concepts of extracellular matrix remodelling in tumour progression and metastasis
Winkler, J., Abisoye-Ogunniyan, A., Metcalf, K. J., & Werb, Z. (2020) · Nature Communications · doi:10.1038/s41467-020-18794-x · Cited by 2,296 · see citing works
Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis
Kim, S., Takahashi, H., Lin, W.-W., Descargues, P., Grivennikov, S., Kim, Y., Luo, J.-L., & Karin, M. (2009) · Nature · doi:10.1038/nature07623 · Cited by 1,100 · see citing works
Challis, J. R., Lockwood, C. J., Myatt, L., Norman, J. E., Strauss, J. F., & Petraglia, F. (2009) · Reproductive Sciences · doi:10.1177/1933719108329095 · Cited by 893 · see citing works
Hyaluronan in Tissue Injury and Repair
Jiang, D., Liang, J., & Noble, P. W. (2007) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.23.090506.123337 · Cited by 835 · see citing works
Characterization of Heme as Activator of Toll-like Receptor 4
Figueiredo, R. T., Fernandez, P. L., Mourao-Sa, D. S., Porto, B. N., Dutra, F. F., Alves, L. S., Oliveira, M. F., Oliveira, P. L., Graça-Souza, A. V., & Bozza, M. T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610737200 · Cited by 576 · see citing works
Abdollahi-Roodsaz, S., Joosten, L. A. B., Koenders, M. I., Devesa, I., Roelofs, M. F., Radstake, T. R. D. J., Heuvelmans-Jacobs, M., Akira, S., Nicklin, M. J. H., Ribeiro-Dias, F., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32639 · Cited by 527 · see citing works
The good and the bad collagens of fibrosis – Their role in signaling and organ function
Karsdal, M. A., Nielsen, S. H., Leeming, D. J., Langholm, L. L., Nielsen, M. J., Manon-Jensen, T., Siebuhr, A., Gudmann, N. S., Rønnow, S., Sand, J. M., et al. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.07.014 · Cited by 509 · see citing works
Novel functions of TIMPs in cell signaling
Chirco, R., Liu, X.-W., Jung, K.-K., & Kim, H.-R. C. (2006) · Cancer and Metastasis Reviews · doi:10.1007/s10555-006-7893-x · Cited by 401 · see citing works
Merline, R., Moreth, K., Beckmann, J., Nastase, M. V., Zeng-Brouwers, J., Tralhão, J. G., Lemarchand, P., Pfeilschifter, J., Schaefer, R. M., Iozzo, R. V., et al. (2011) · Science Signaling · doi:10.1126/scisignal.2001868 · Cited by 333 · see citing works
Self-citationDAMPs as mediators of sterile inflammation in aging-related pathologies
Feldman, N., Rotter-Maskowitz, A., & Okun, E. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.01.003 · Cited by 283 · see citing works
Danger-associated molecular patterns in Alzheimer’s disease
Venegas, C., & Heneka, M. T. (2017) · Journal of Leukocyte Biology · doi:10.1189/jlb.3mr0416-204r · Cited by 236 · see citing works
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Kopp, R., Krautloher, A., Ramírez-Fernández, A., & Nicke, A. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00183 · Cited by 217 · see citing works
Toll-Like Receptors: Regulators of the Immune Response in the Human Gut
Hug, H., Mohajeri, M., & La Fata, G. (2018) · Nutrients · doi:10.3390/nu10020203 · Cited by 217 · see citing works
Moreth, K., Brodbeck, R., Babelova, A., Gretz, N., Spieker, T., Zeng-Brouwers, J., Pfeilschifter, J., Young, M. F., Schaefer, R. M., & Schaefer, L. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42213 · Cited by 207 · see citing works
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Innate Immune Cell Trafficking and Function During Sterile Inflammation of the Liver
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Versican in inflammation and tissue remodeling: The impact on lung disorders
Andersson-Sjoland, A., Hallgren, O., Rolandsson, S., Weitoft, M., Tykesson, E., Larsson-Callerfelt, A.-K., Rydell-Tormanen, K., Bjermer, L., Malmstrom, A., Karlsson, J. C., et al. (2015) · Glycobiology · doi:10.1093/glycob/cwu120 · Cited by 98 · see citing works
Song, R., Zeng, Q., Ao, L., Yu, J. A., Cleveland, J. C., Zhao, K.-S., Fullerton, D. A., & Meng, X. (2012) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.112.300116 · Cited by 86 · see citing works
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Derbali, H., Bossé, Y., Côté, N., Pibarot, P., Audet, A., Pépin, A., Arsenault, B., Couture, C., Després, J.-P., & Mathieu, P. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.090541 · Cited by 71 · see citing works
Massey, V. L., Dolin, C. E., Poole, L. G., Hudson, S. V., Siow, D. L., Brock, G. N., Merchant, M. L., Wilkey, D. W., & Arteel, G. E. (2017) · Hepatology · doi:10.1002/hep.28918 · Cited by 64 · see citing works
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Song, R., Ao, L., Zhao, K.-S., Zheng, D., Venardos, N., Fullerton, D. A., & Meng, X. (2014) · Inflammation Research · doi:10.1007/s00011-014-0743-3 · Cited by 37 · see citing works
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“ECM-bioscaffold degradation products function as damage-associated molecular patterns (DAMPs) that ligate pattern-recognition and scavenger receptors on dendritic cells and macrophages; in some contexts, they also signal via integrins [2,26,28,29].”
- Authors
- Schaefer, L., Babelova, A., Kiss, E., Hausser, H.-J., Baliova, M., Krzyzankova, M., Marsche, G., Young, M. F., Mihalik, D., Götte, M., Malle, E., Schaefer, R. M., & Gröne, H.-J.
- Affiliations
- University of Münster (DE)
- Universität Ulm (DE)
- Medical University of Graz (AT)
- National Institutes of Health (US)
- German Cancer Research Center (DE)
- Corresponding author
- Schaefer, Liliana
- Venue
- Journal of Clinical Investigation
- Published
- 2005-08-01
- Volume
- 115
- Issue
- 8
- Pages
- 2223-2233
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1174916
- OpenAlex
- W1987383242
- Cited by
- 850
- References
- 59
- Citations by year
- 2026: 22 · 2025: 35 · 2024: 16 · 2023: 35 · 2022: 40 · 2021: 49 · 2020: 44 · 2019: 34 · 2018: 44 · 2017: 41 · 2016: 49 · 2015: 52 · 2014: 49 · 2013: 49 · 2012: 56
- FWCI
- 11.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts Institute of Technology
- Deutsches Krebsforschungszentrum
- Deutsche Forschungsgemeinschaft (SFB 492, SFB405)
- Austrian Science Fund (P17013)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Keywords
- biglycan, small leucine-rich proteoglycans, extracellular matrix, TLR4, TLR2, macrophages, innate immunity, pro-inflammatory signaling, TNF-α, CXCL2, NF-κB, p38 MAPK, ERK, sepsis, LPS, zymosan, MyD88, endogenous ligands
- MeSH terms
- Animals, Antigens, Differentiation, Extracellular Matrix, Inflammation, Lipopolysaccharides, Lung, Membrane Glycoproteins, Proteoglycans, Receptors, Cell Surface, Receptors, Immunologic, Tumor Necrosis Factor-alpha, Zymosan, Signal Transduction, Extracellular Matrix Proteins, NF-kappa B, Macrophages, Alveolar, Mice, Knockout, Sepsis, p38 Mitogen-Activated Protein Kinases, Adaptor Proteins, Signal Transducing, Toll-Like Receptors, Toll-Like Receptor 2, Toll-Like Receptor 4, Mice, Myeloid Differentiation Factor 88, Biglycan
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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