MFG-E8 and HMGB1 Are Involved in the Mechanism Underlying Alcohol-Induced Impairment of Macrophage Efferocytosis

Wang, Xiao; Bu, Heng Fu; Zhong, Wei; Asai, Akihiro; Zhou, Zhanxiang; Tan, Xiao Di

doi:10.2119/molmed.2012.00260

Cited by 32 publications

(44 citation statements)

References 49 publications

(84 reference statements)

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“…Efferocytosis dysfunction may lead to excessive accumulation of late apoptotic and/or secondary necrotic cells and subsequent inflammatory response. Compared with milk fat globule-EGF factor 8 (MFG-E8) (Miksa et al, 2009; Wang et al, 2013k), HMGB1 is a negative regulator of efferocytosis by its C-terminal acidic tail (Banerjee et al, 2010) and poly(ADP-ribosyl)ation (Davis et al, 2012b). Extracellular HMGB1 inhibits efferocytosis by binding phosphatidylserine or α ν β 3 integrin in apoptotic neutrophils or phagocytic macrophages, respectively (Friggeri et al, 2010; Liu et al, 2008a).…”

Section: Hmgb1 Functionmentioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

802

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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Section: Hmgb1 Functionmentioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

802

828

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“…Twenty-four hours after transfection, cells were treated with LPS (100 ng/ml) or vehicle (i.e. control) for 24 h and luciferase assay was performed with a standard protocol as previously described [Wang et al, 2013]. We found that the relative luciferase activity was reduced by 38.7 ± 1.1 % in pGL3-444/+146-transfected cells and 23.4 ± 0.47% in pGL3-94/+146-transfected cells 24 h after LPS treatment ( P <0.05) compared to control cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Murine peritoneal macrophages were isolated using a standard protocol in our lab [Bu et al, 2006; Wang et al, 2013]. The procedure was conducted according to the Materials and Methods approved by the Institutional Animal Care and Use Committee.…”

Section: Methodsmentioning

confidence: 99%

“…Quantitative real-time PCR for measuring MFG-E8 gene transcripts was performed using a standard protocol as previously described [Wang et al, 2013]. Sequences of forward (F) and reverse (R) primers for real-time PCR were murine MFG-E8F 5′-ATCTACTGCCTCTGCCCTGA-3′, murine MFG-E8R 5′-CCAGACATTTGGCATCATTG-3′, murine 18S rRNAF 5′-TGCCCTATCAACTTTCGATG-3′, and murine 18S rRNAR 5′-GATGTGGTAGCCGTTTCTCA-3′.…”

Section: Methodsmentioning

confidence: 99%

“…Down-regulation of MFG-E8 has been shown in acute inflammatory conditions such as sepsis, ischemia/reperfusion, and acute alcohol exposure [Bu et al, 2007; Miksa et al, 2006; Wang et al, 2013]. On the other hand, MFG-E8 level was found to be increased during the development of tissue fibrosis and obesity [Atabai et al, 2009; Khalifeh-Soltani et al, 2014].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Mechanisms Underlying the Regulation of the MFG‐E8 Gene Promoter Activity in Physiological and Inflammatory Conditions

Wang

Liu

et al. 2015

J of Cellular Biochemistry

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Milk fat globule-EGF factor 8 (MFG-E8) is expressed by macrophages and plays an important role in attenuating inflammation and maintaining tissue homeostasis. Previously, we and others found that LPS inhibits MFG-E8 gene expression in macrophages. Here, we characterized the 5′-flanking region of the mouse MFG-E8 gene. To functionally analyze the upstream regulatory region of the MFG-E8 gene, a series of luciferase reporter gene constructs containing deleted or mutated regulatory elements were prepared. Using the luciferase assay, we revealed that Sp1 binding motifs within the proximal promoter region were necessary for full activity of the MFG-E8 promoter, whereas AP-1 like binding sequence at −372 played a role in governing the promoter activity at a homeostatic level. With chromatin immunoprecipitation assay, we showed that Sp1 and c-Jun physically interact with the MFG-E8 promoter region in vivo. In addition, Sp1 was found to regulate the MFG-E8 promoter activity positively and c-Jun negatively. Furthermore, we demonstrated that LPS inhibited MFG-E8 promoter activity via targeting Sp1 and AP-1-like motifs in the 5′-flanking region. Collectively, our data indicate that Sp1 and AP-1-related factors are involved in the regulation of MFG-E8 gene transcription by targeting their binding sites in the 5′-flanking region under physiological and inflammatory states.

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High‐Mobility Group Box‐1 and Liver Disease

Gaskell

Nieto

2018

Hepatology Communications

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High‐mobility group box‐1 (HMGB1) is a ubiquitous protein. While initially thought to be simply an architectural protein due to its DNA‐binding ability, evidence from the last decade suggests that HMGB1 is a key protein participating in the pathogenesis of acute liver injury and chronic liver disease. When it is passively released or actively secreted after injury, HMGB1 acts as a damage‐associated molecular pattern that communicates injury and inflammation to neighboring cells by the receptor for advanced glycation end products or toll‐like receptor 4, among others. In the setting of acute liver injury, HMGB1 participates in ischemia/reperfusion, sepsis, and drug‐induced liver injury. In the context of chronic liver disease, it has been implicated in alcoholic liver disease, liver fibrosis, nonalcoholic steatohepatitis, and hepatocellular carcinoma. Recently, specific posttranslational modifications have been identified that could condition the effects of the protein in the liver. Here, we provide a detailed review of how HMGB1 signaling participates in acute liver injury and chronic liver disease.

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MFG-E8 and HMGB1 Are Involved in the Mechanism Underlying Alcohol-Induced Impairment of Macrophage Efferocytosis

Cited by 32 publications

References 49 publications

HMGB1 in health and disease

HMGB1 in health and disease

Molecular Mechanisms Underlying the Regulation of the MFG‐E8 Gene Promoter Activity in Physiological and Inflammatory Conditions

High‐Mobility Group Box‐1 and Liver Disease

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