ANGPTL2 Induces Synovial Inflammation via LILRB2

Nishiyama, Sayuri; Hirose, Naoto; Yanoshita, Makoto; Takano, Mami; Kubo, Naoki; Yamauchi, Yuka; Onishi, Azusa; Ito, Sotaro; Sakata, Shuzo; Kita, Daiki; Asakawa-Tanne, Yuki; Tanimoto, Kotaro

doi:10.1007/s10753-020-01406-7

Cited by 11 publications

(13 citation statements)

References 41 publications

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“…The nuclear factor-κB (NF-κB) is a transcription factor that develops a pivotal role in activating both innate and adaptive immunity, mainly leading to target cells to increase production of proinflammatory cytokines [ 33 ], such as IL-1β, TNFα and IL-6. The activation via receptors such as integrin α5β1 and leukocyte immunoglobulin-like receptor B2 would trigger a transduction signaling cascade increasing expression of inflammatory factors genes through NF-κB and other transcription factors, as has been demonstrated in synovial tissue [ 34 ]. NF-κB pathway activation has been associated with several inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and asthma [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Angiopoietin-like 2 Protein and Hidradenitis Suppurativa: A New Biomarker for Disease Severity

et al. 2023

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Hidradenitis suppurativa (HS) is a chronic inflammatory disease whose pathogenesis is not fully understood at present. The role of proinflammatory cytokines, several adipokines, retinol-binding protein 4, angiopoietin-2 and other molecules has been previously reported. Angiopoietin-like 2 protein (ANGPTL2) is a glycoprotein belonging to the angiopoietin-like family that may play a pivotal role in the pathogenesis of several chronic inflammatory diseases. To our knowledge, the role of serum ANGPTL2 levels in HS has not been assessed to date. In the current case–control study, we aimed to investigate serum ANGPTL2 levels in HS patients and controls and to assess whether ANGPTL2 levels could be associated with the severity of HS. Ninety-four patients with HS and sixty controls of similar age and sex were included in the study. Demographic, anthropometric, and clinical data, as well as routine laboratory parameters and serum concentrations of ANGPTL2, were assessed in all participants. HS patients had significantly higher serum ANGPTL2 levels than controls after adjusting for confounders. Moreover, ANGPTL2 concentrations positively correlated with disease duration and severity. Our results indicate for the first time that serum ANGPTL2 concentrations are elevated in HS patients compared to controls and correlate with the duration of the disease. Besides, ANGPTL2 might serve as a biomarker of HS severity.

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Section: Discussionmentioning

confidence: 99%

Angiopoietin-like 2 Protein and Hidradenitis Suppurativa: A New Biomarker for Disease Severity

et al. 2023

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“…ANGPTL2 has been reported to regulate inflammation in multiple diseases, such as osteoarthritis [ 50 , 51 ], atherosclerosis [ 52 ], acute lung injury [ 53 ] and obesity [ 17 ]. ANGPTL2 promotes vascular inflammation and causes endothelial dysfunction and atherosclerotic progression via activation of pro-inflammatory signaling in endothelial cells, enhancement of macrophage infiltration [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of hypoxia-inducible factor 1-alpha (HIF1α) interferes with angiopoietin-like protein 2 (ANGPTL2) to attenuate high glucose-triggered hypoxia/reoxygenation injury in cardiomyocytes

Chen

Wang

et al. 2022

Bioengineered

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To investigate the role of hypoxia-inducible factor 1-alpha (HIF1A) in hypoxia/reoxygenation (H/R) injury of cardiomyocytes induced by high glucose (HG). The in vitro model of coronary heart disease with diabetes was that H9c2 cells were stimulated by H/R and HG. Quantitative reverse transcription PCR (RT-qPCR) and Western blot analysis were used to detect the expression of HIF1A and angiopoietin-like protein 2 (ANGPTL2) in H9c2 cells. Cell viability and apoptosis were, respectively, estimated by Cell Counting Kit 8 (CCK-8) and TUNEL assays. Lactate dehydrogenase (LDH) activity, inflammation and oxidative stress were in turn detected by their commercial assay kits. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were used to confirm the association between HIF1A and ANGPTL2 promoter. The expression of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway-related proteins and apoptosis-related proteins were also detected by Western blot analysis. As a result, ANGPTL2 expression was upregulated in H9c2 cells induced by HG or/and H/R. ANGPTL2 positively modulated HIF1A expression in H9c2 cells. HG or/and H/R suppressed the cell viability and promoted apoptosis, inflammatory response and oxidative stress levels in H9c2 cells. However, the knockdown of ANGPTL2 could reverse the above phenomena in H/R-stimulated-H9c2 cells through activation of Nrf2/HO-1 pathway. HIF1A transcriptionally activated ANGPTL2 expression. The effect of knockdown of ANGPTL2 on H/R triggered-H9c2 cells was weakened by HIF1A overexpression. In conclusion, knockdown of HIF1A downregulated ANGPTL2 to alleviate H/R injury in HG-induced H9c2 cells by activating the Nrf2/HO-1 pathway.

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Section: Angptls and Inflammationmentioning

confidence: 99%

“…ANGPTLs are involved in multiple inflammatory diseases including metabolic syndrome (Tabata et al, 2009), acute organ injuries (Amadatsu et al, 2016; Guo et al, 2015; Yang et al, 2018; Zheng et al, 2021), chronic organ/tissue injuries or repair (Cho et al, 2019; Nishiyama et al, 2021; Okada et al, 2010), cancer progression (Aoi et al, 2011; Gao et al, 2015; Sasaki et al, 2012) and other inflammation‐related diseases (Tanigawa et al, 2016). Several studies have indicated that the effects of ANGPTLs in these diseases are mediated by both their classical roles in modulating lipid metabolism or angiogenesis and via regulating inflammation (Aryal et al, 2016; Li et al, 2019; Morinaga et al, 2016; Thorin‐Trescases & Thorin, 2017).…”

Section: Angptls and Inflammationmentioning

confidence: 99%

Emerging roles of angiopoietin‐like proteins in inflammation: Mechanisms and potential as pharmacological targets

Yang

Song

Niu

et al. 2021

Journal Cellular Physiology

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Angiopoietin-like proteins (ANGPTLs), a family of eight secreted glycoproteins termed ANGTPL1-8, are involved in angiogenesis, lipid metabolism, cancer progression, and inflammation. Their roles in regulating lipid metabolism have been intensively studied, as some ANGPTLs are promising pharmacological targets for hypertriglyceridemia and associated cardiovascular disease. Recently, the emerging roles of ANGPTLs in inflammation have attracted great attention. First, elevated levels of multiple circulating ANGPTLs in inflammatory diseases make them potential disease biomarkers. Second, multiple ANGPTLs regulate acute or chronic inflammation via various mechanisms, including triggering inflammatory signaling through their action as ligands for integrin or forming homo-/hetero-oligomers to regulate signal transduction via extra-or intracellular mechanisms. As dysregulation of the inflammatory response is a critical trigger in many diseases, understanding the roles of ANGPTLs in inflammation will aid in drug/therapy development. Here, we summarize the roles, mechanisms, and potential therapeutic values for ANGPTLs in inflammation and inflammatory diseases.

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ANGPTL2 Induces Synovial Inflammation via LILRB2

Cited by 11 publications

References 41 publications

Angiopoietin-like 2 Protein and Hidradenitis Suppurativa: A New Biomarker for Disease Severity

Angiopoietin-like 2 Protein and Hidradenitis Suppurativa: A New Biomarker for Disease Severity

Knockdown of hypoxia-inducible factor 1-alpha (HIF1α) interferes with angiopoietin-like protein 2 (ANGPTL2) to attenuate high glucose-triggered hypoxia/reoxygenation injury in cardiomyocytes

Emerging roles of angiopoietin‐like proteins in inflammation: Mechanisms and potential as pharmacological targets

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