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The m6A Reader IGF2BP2 Regulates Macrophage Phenotypic Activation and Inflammatory Diseases by Stabilizing TSC1 and PPARγ
Advanced Science ( IF 14.3 ) Pub Date : 2021-05-03 , DOI: 10.1002/advs.202100209 Xia Wang 1 , Yuge Ji 1 , Panpan Feng 2 , Rucheng Liu 1 , Guosheng Li 2 , Junjie Zheng 1 , Yaqiang Xue 3 , Yaxun Wei 4 , Chunyan Ji 2 , Dawei Chen 5 , Jingxin Li 1
Advanced Science ( IF 14.3 ) Pub Date : 2021-05-03 , DOI: 10.1002/advs.202100209 Xia Wang 1 , Yuge Ji 1 , Panpan Feng 2 , Rucheng Liu 1 , Guosheng Li 2 , Junjie Zheng 1 , Yaqiang Xue 3 , Yaxun Wei 4 , Chunyan Ji 2 , Dawei Chen 5 , Jingxin Li 1
Affiliation
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Phenotypic polarization of macrophages is regulated by a milieu of cues in the local tissue microenvironment. Currently, little is known about how the intrinsic regulators modulate proinflammatory (M1) versus prohealing (M2) macrophages activation. Here, it is observed that insulin-like growth factor 2 messenger RNA (mRNA)-binding protein 2 (IGF2BP2)-deleted macrophages exhibit enhanced M1 phenotype and promote dextran sulfate sodium induced colitis development. However, the IGF2BP2−/− macrophages are refractory to interleukin-4 (IL-4) induced activation and alleviate cockroach extract induced pulmonary allergic inflammation. Molecular studies indicate that IGF2BP2 switches M1 macrophages to M2 activation by targeting tuberous sclerosis 1 via an N6-methyladenosine (m6A)-dependent manner. Additionally, it is also shown a signal transducer and activators of transcription 6 (STAT6)-high mobility group AT-hook 2-IGF2BP2-peroxisome proliferator activated receptor-γ axis involves in M2 macrophages differentiation. These findings highlight a key role of IGF2BP2 in regulation of macrophages activation and imply a potential therapeutic target of macrophages in the inflammatory diseases.
中文翻译：
m6A Reader IGF2BP2 通过稳定 TSC1 和 PPARγ 来调节巨噬细胞表型激活和炎症性疾病
巨噬细胞的表型极化受到局部组织微环境中的环境因素的调节。目前，人们对内在调节因子如何调节促炎 (M1) 与促愈合 (M2) 巨噬细胞激活知之甚少。在此，观察到胰岛素样生长因子 2 信使 RNA (mRNA) 结合蛋白 2 (IGF2BP2) 缺失的巨噬细胞表现出增强的 M1 表型，并促进葡聚糖硫酸钠诱导的结肠炎的发展。然而，IGF2BP2 −/−巨噬细胞对白细胞介素 4 (IL-4) 诱导的激活具有抵抗力，并能减轻蟑螂提取物诱导的肺部过敏性炎症。分子研究表明，IGF2BP2 通过 N6-甲基腺苷 (m 6 A) 依赖性方式靶向结节性硬化症 1，从而将 M1 巨噬细胞转变为 M2 激活。此外，还显示信号转导器和转录激活剂6（STAT6）-高迁移率组AT-hook 2-IGF2BP2-过氧化物酶体增殖物激活受体-γ轴参与M2巨噬细胞分化。这些发现强调了 IGF2BP2 在调节巨噬细胞活化中的关键作用，并暗示巨噬细胞在炎症性疾病中的潜在治疗靶点。
更新日期：2021-07-07
中文翻译：
m6A Reader IGF2BP2 通过稳定 TSC1 和 PPARγ 来调节巨噬细胞表型激活和炎症性疾病
巨噬细胞的表型极化受到局部组织微环境中的环境因素的调节。目前，人们对内在调节因子如何调节促炎 (M1) 与促愈合 (M2) 巨噬细胞激活知之甚少。在此，观察到胰岛素样生长因子 2 信使 RNA (mRNA) 结合蛋白 2 (IGF2BP2) 缺失的巨噬细胞表现出增强的 M1 表型，并促进葡聚糖硫酸钠诱导的结肠炎的发展。然而，IGF2BP2 −/−巨噬细胞对白细胞介素 4 (IL-4) 诱导的激活具有抵抗力，并能减轻蟑螂提取物诱导的肺部过敏性炎症。分子研究表明，IGF2BP2 通过 N6-甲基腺苷 (m 6 A) 依赖性方式靶向结节性硬化症 1，从而将 M1 巨噬细胞转变为 M2 激活。此外，还显示信号转导器和转录激活剂6（STAT6）-高迁移率组AT-hook 2-IGF2BP2-过氧化物酶体增殖物激活受体-γ轴参与M2巨噬细胞分化。这些发现强调了 IGF2BP2 在调节巨噬细胞活化中的关键作用，并暗示巨噬细胞在炎症性疾病中的潜在治疗靶点。
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