PMC:7335494 / 17285-19479 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7335494","sourcedb":"PMC","sourceid":"7335494","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7335494","text":"Osteopontin, an ECM glycoprotein, excessively secreted by adipose tissue macrophages (Nomiyama et al., 2007) enhances adipose tissue inflammation and facilitates the onset of insulin resistance (Aouadi et al., 2013). Another important ECM component, the glycosaminoglycan HA, has been strongly correlated to increased inflammatory burden, including cancer-associated (Nikitovic et al., 2015) and sterile inflammation (Kavasi et al., 2017, 2019; Nikitovic et al., 2014b). The biologic role of HA is dependent on its size. Thus, high molecular weight HA (HMWHA), physiologically secreted by cells facilitates normal tissue stability (Kavasi et al., 2017). In contrast, low molecular weight HA (LMWHA) fragments, produced via enzymatic action or chemical reactions, are pro-inflammatory and have been characterized as a danger-associated molecular patterns (DAMP) (Kavasi et al., 2017, 2019; Nikitovic et al., 2014a). Indeed, the generated LMWHA fragments can trigger a Toll-like receptor 4 (TLR4)/NF-κB signalling pathway to regulate inflammatory genes transcription in immune cells (Kavasi et al., 2017; Termeer et al., 2002). Interestingly, HA levels were increased in various tissues of type-2 diabetes mellius (T2DM), but not in type-1 (T1DM) subjects, and independent of glycaemic control. Taking into account that T2DM, in contrast to T1DM, is linked with systemic inflammation, it was suggested that inflammatory factors and not hyperglycaemia upregulate HA levels (Nagy et al., 2019). Importantly, it was demonstrated that the expression of genes involved in the metabolism of HA was positively correlated to the process of adipocyte differentiation (Allingham et al., 2006). Recently, it was shown that HA exerts inhibitory effects in vitro regarding adipogenesis of 3T3-L1 cells, whereas downregulating HA prevented insulin resistance and NAFLD correlated to excess deposition of abdominal fat in HFD-feeding C57BL/6J mouse model (Ji et al., 2014). Moreover, treatment of HFD-fed obese mice with a stable hyaluronidase complex, where human recombinant hyaluronidase was Pegylated, was shown to decreases adiposity, adipose tissue inflammation and insulin resistance (Kang et al., 2013).","tracks":[{"project":"LitCovid_Glycan-Motif-Structure","denotations":[{"id":"T5","span":{"begin":272,"end":274},"obj":"https://glytoucan.org/Structures/Glycans/G00017MO"},{"id":"T6","span":{"begin":492,"end":494},"obj":"https://glytoucan.org/Structures/Glycans/G00017MO"},{"id":"T7","span":{"begin":549,"end":551},"obj":"https://glytoucan.org/Structures/Glycans/G00017MO"},{"id":"T8","span":{"begin":688,"end":690},"obj":"https://glytoucan.org/Structures/Glycans/G00017MO"},{"id":"T9","span":{"begin":1141,"end":1143},"obj":"https://glytoucan.org/Structures/Glycans/G00017MO"},{"id":"T10","span":{"begin":1460,"end":1462},"obj":"https://glytoucan.org/Structures/Glycans/G00017MO"},{"id":"T11","span":{"begin":1583,"end":1585},"obj":"https://glytoucan.org/Structures/Glycans/G00017MO"},{"id":"T12","span":{"begin":1710,"end":1712},"obj":"https://glytoucan.org/Structures/Glycans/G00017MO"},{"id":"T13","span":{"begin":1811,"end":1813},"obj":"https://glytoucan.org/Structures/Glycans/G00017MO"}],"attributes":[{"subj":"T5","pred":"source","obj":"LitCovid_Glycan-Motif-Structure"},{"subj":"T6","pred":"source","obj":"LitCovid_Glycan-Motif-Structure"},{"subj":"T7","pred":"source","obj":"LitCovid_Glycan-Motif-Structure"},{"subj":"T8","pred":"source","obj":"LitCovid_Glycan-Motif-Structure"},{"subj":"T9","pred":"source","obj":"LitCovid_Glycan-Motif-Structure"},{"subj":"T10","pred":"source","obj":"LitCovid_Glycan-Motif-Structure"},{"subj":"T11","pred":"source","obj":"LitCovid_Glycan-Motif-Structure"},{"subj":"T12","pred":"source","obj":"LitCovid_Glycan-Motif-Structure"},{"subj":"T13","pred":"source","obj":"LitCovid_Glycan-Motif-Structure"}]},{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T140","span":{"begin":16,"end":19},"obj":"Body_part"},{"id":"T141","span":{"begin":20,"end":32},"obj":"Body_part"},{"id":"T142","span":{"begin":58,"end":72},"obj":"Body_part"},{"id":"T143","span":{"begin":73,"end":84},"obj":"Body_part"},{"id":"T144","span":{"begin":118,"end":132},"obj":"Body_part"},{"id":"T145","span":{"begin":175,"end":182},"obj":"Body_part"},{"id":"T146","span":{"begin":235,"end":238},"obj":"Body_part"},{"id":"T147","span":{"begin":254,"end":271},"obj":"Body_part"},{"id":"T148","span":{"begin":272,"end":274},"obj":"Body_part"},{"id":"T149","span":{"begin":492,"end":494},"obj":"Body_part"},{"id":"T150","span":{"begin":549,"end":551},"obj":"Body_part"},{"id":"T151","span":{"begin":589,"end":594},"obj":"Body_part"},{"id":"T152","span":{"begin":614,"end":620},"obj":"Body_part"},{"id":"T153","span":{"begin":688,"end":690},"obj":"Body_part"},{"id":"T154","span":{"begin":1075,"end":1080},"obj":"Body_part"},{"id":"T155","span":{"begin":1141,"end":1143},"obj":"Body_part"},{"id":"T156","span":{"begin":1177,"end":1184},"obj":"Body_part"},{"id":"T157","span":{"begin":1460,"end":1462},"obj":"Body_part"},{"id":"T158","span":{"begin":1583,"end":1585},"obj":"Body_part"},{"id":"T159","span":{"begin":1630,"end":1639},"obj":"Body_part"},{"id":"T160","span":{"begin":1710,"end":1712},"obj":"Body_part"},{"id":"T161","span":{"begin":1781,"end":1786},"obj":"Body_part"},{"id":"T162","span":{"begin":1811,"end":1813},"obj":"Body_part"},{"id":"T163","span":{"begin":1824,"end":1831},"obj":"Body_part"},{"id":"T164","span":{"begin":2123,"end":2137},"obj":"Body_part"},{"id":"T165","span":{"begin":2155,"end":2162},"obj":"Body_part"}],"attributes":[{"id":"A140","pred":"fma_id","subj":"T140","obj":"http://purl.org/sig/ont/fma/fma9672"},{"id":"A141","pred":"fma_id","subj":"T141","obj":"http://purl.org/sig/ont/fma/fma62925"},{"id":"A142","pred":"fma_id","subj":"T142","obj":"http://purl.org/sig/ont/fma/fma20110"},{"id":"A143","pred":"fma_id","subj":"T143","obj":"http://purl.org/sig/ont/fma/fma63261"},{"id":"A144","pred":"fma_id","subj":"T144","obj":"http://purl.org/sig/ont/fma/fma20110"},{"id":"A145","pred":"fma_id","subj":"T145","obj":"http://purl.org/sig/ont/fma/fma83365"},{"id":"A146","pred":"fma_id","subj":"T146","obj":"http://purl.org/sig/ont/fma/fma9672"},{"id":"A147","pred":"fma_id","subj":"T147","obj":"http://purl.org/sig/ont/fma/fma63011"},{"id":"A148","pred":"fma_id","subj":"T148","obj":"http://purl.org/sig/ont/fma/fma63014"},{"id":"A149","pred":"fma_id","subj":"T149","obj":"http://purl.org/sig/ont/fma/fma63014"},{"id":"A150","pred":"fma_id","subj":"T150","obj":"http://purl.org/sig/ont/fma/fma63014"},{"id":"A151","pred":"fma_id","subj":"T151","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A152","pred":"fma_id","subj":"T152","obj":"http://purl.org/sig/ont/fma/fma9637"},{"id":"A153","pred":"fma_id","subj":"T153","obj":"http://purl.org/sig/ont/fma/fma63014"},{"id":"A154","pred":"fma_id","subj":"T154","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A155","pred":"fma_id","subj":"T155","obj":"http://purl.org/sig/ont/fma/fma63014"},{"id":"A156","pred":"fma_id","subj":"T156","obj":"http://purl.org/sig/ont/fma/fma9637"},{"id":"A157","pred":"fma_id","subj":"T157","obj":"http://purl.org/sig/ont/fma/fma63014"},{"id":"A158","pred":"fma_id","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