High-mobility group box-1 and its role in angiogenesis

Yang, Shuai; Xu, Ling; Yang, Tianshu; Wang, Fang

doi:10.1189/jlb.0713412

Cited by 82 publications

(71 citation statements)

References 150 publications

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“…Importantly, IRF5 occupancy on the CDH5 promoter was enhanced by TLR4 activation. Together with the evidence that TLR4 and its endogenous ligands have been implicated in angiogenesis (27,28), the present data provide a previously unidentified insight into the role of IRF5 in TLR4-mediated angiogenesis and suggest that the TLR4-IRF5 axis potentially regulates vascular features of SSc.…”

Section: Discussionmentioning

confidence: 79%

Multifaceted contribution of the TLR4-activated IRF5 transcription factor in systemic sclerosis

Saigusa

Asano

Taniguchi

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Systemic sclerosis (SSc) is a multisystem autoimmune disorder with clinical manifestations resulting from tissue fibrosis and extensive vasculopathy. A potential disease susceptibility gene for SSc is IFN regulatory factor 5 (IRF5), whose SNP is associated with milder clinical manifestations; however, the underlying mechanisms of this association remain elusive. In this study we examined IRF5-deficient (Irf5−/−) mice in the bleomycin-treated SSc murine model. We show that dermal and pulmonary fibrosis induced by bleomycin is attenuated in Irf5−/− mice. Interestingly, we find that multiple SSc-associated events, such as fibroblast activation, inflammatory cell infiltration, endothelial-to-mesenchymal transition, vascular destabilization, Th2/Th17 skewed immune polarization, and B-cell activation, are suppressed in these mice. We further provide evidence that IRF5, activated by Toll-like receptor 4 (TLR4), binds to the promoters of various key genes involved in SSc disease pathology. These observations are congruent with the high level of expression of IRF5, TLR4, and potential endogenous TLR4 ligands in SSc skin lesions. Our study sheds light on the TLR4-IRF5 pathway in the pathology of SSc with clinical implications of targeting the IRF5 pathways in the suppression of disease development.

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Section: Discussionmentioning

confidence: 79%

Multifaceted contribution of the TLR4-activated IRF5 transcription factor in systemic sclerosis

Saigusa

Asano

Taniguchi

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Most of these evidences have been raised from the effects of HMGB1 on tumor cells themselves [26,40,41]. However, the effects of HMGB1 on other cellular components of tumor stroma and whether this stimulation may favor tumor-supporting processes have remained mostly elusive.…”

Section: Discussionmentioning

confidence: 98%

HMGB1 enhances the protumoral activities of M2 macrophages by a RAGE-dependent mechanism

et al. 2015

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The monocyte-macrophage lineage shows a high degree of diversity and plasticity. Once they infiltrate tissues, they may acquire two main functional phenotypes, being known as the classically activated type 1 macrophages (M1) and the alternative activated type 2 macrophages (M2). The M1 phenotype can be induced by bacterial products and interferon-γ and exerts a cytotoxic effect on cancer cells. Conversely, the alternatively activated M2 phenotype is induced by Il-4/IL13 and promotes tumor cell growth and vascularization. Although receptor for advanced glycation end-products (RAGE) engagement in M1 macrophages has been reported by several groups to promote inflammation, nothing is known about the functionality of RAGE in M2 macrophages. In the current study, we demonstrate that RAGE is equally expressed in both macrophage phenotypes and that RAGE activation by high-mobility group protein box1 (HMGB1) promotes protumoral activities of M2 macrophages. MKN45 cells co-cultured with M2 macrophages treated with HMGB1 at different times displayed higher invasive abilities. Additionally, conditioned medium from HMGB1-treated M2 macrophages promotes angiogenesis in vitro. RAGE-targeting knockdown abrogates these activities. Overall, the present findings suggest that HMGB1 may contribute, by a RAGE-dependent mechanism, to the protumoral activities of the M2 phenotype.

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“…Two major signalling pathways are involved [26]: (i) MAP kinase signalling, including Erk and JNK, which ultimately lead to the activation of NF-κB, and (ii) the Rho-family small GTPase CDC42/Rac and MMP-2/-9 pathway, which is well known as a regulator of cell remodelling and motility. In several cancer models, it has been reported that HMGB1 is related to the expression of MMP-2/-9 [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

High-mobility group Box 1: A novel inducer of the epithelial–mesenchymal transition in colorectal carcinoma

Zhu

Chen

et al. 2015

Cancer Letters

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High-mobility group box-1 and its role in angiogenesis

Cited by 82 publications

References 150 publications

Multifaceted contribution of the TLR4-activated IRF5 transcription factor in systemic sclerosis

Multifaceted contribution of the TLR4-activated IRF5 transcription factor in systemic sclerosis

HMGB1 enhances the protumoral activities of M2 macrophages by a RAGE-dependent mechanism

High-mobility group Box 1: A novel inducer of the epithelial–mesenchymal transition in colorectal carcinoma

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