MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E2-mediated M2 generation.
MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E2-mediated M2 generation.
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DOI：
10.1371/journal.pone.0115855
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Serezani CH
中科院分区：
文献类型：
--
作者：
Wang Z;Brandt S;Medeiros A;Wang S;Wu H;Dent A;Serezani CH
巨噬细胞决定炎症的发生和消退。在急性炎症期间，经典活化的巨噬细胞（M1）占主导地位，在消退期，替代性巨噬细胞（M2）占主导地位。参与巨噬细胞极化的分子机制尚未得到充分研究。MicroRNA在M1和M2巨噬细胞中差异表达，影响巨噬细胞极化。我们确定了miR-21在巨噬细胞极化中的作用，并发现miR-21和脂质介质前列腺素E2（PGE 2）之间的串扰是巨噬细胞极化的决定因素。miR-21抑制会损害M2特征基因的表达，但不会损害M1基因的表达。PGE 2及其下游效应物PKA和Epac抑制miR-21的表达并增强M2基因的表达，并且这种作用在miR-21-/-细胞中更明显。在参与巨噬细胞极化的潜在靶点中，我们发现STAT 3和SOCS 1在miR-21-/-细胞中增强，并被PGE 2进一步增强。我们发现STAT 3是巨噬细胞中miR-21的直接靶点。沉默STAT 3基因消除了PGE 2介导的miR-21-/-巨噬细胞中M2基因的表达。这些数据揭示了参与稳态巨噬细胞极化的分子制动器，并提出了预防炎症反应的新治疗策略。
Macrophages dictate both initiation and resolution of inflammation. During acute inflammation classically activated macrophages (M1) predominate, and during the resolution phase alternative macrophages (M2) are dominant. The molecular mechanisms involved in macrophage polarization are understudied. MicroRNAs are differentially expressed in M1 and M2 macrophages that influence macrophage polarization. We identified a role of miR-21 in macrophage polarization, and found that cross-talk between miR-21 and the lipid mediator prostaglandin E2 (PGE2) is a determining factor in macrophage polarization. miR-21 inhibition impairs expression of M2 signature genes but not M1 genes. PGE2 and its downstream effectors PKA and Epac inhibit miR-21 expression and enhance expression of M2 genes, and this effect is more pronounced in miR-21-/- cells. Among potential targets involved in macrophage polarization, we found that STAT3 and SOCS1 were enhanced in miR-21-/- cells and further enhanced by PGE2. We found that STAT3 was a direct target of miR-21 in macrophages. Silencing the STAT3 gene abolished PGE2-mediated expression of M2 genes in miR-21-/- macrophages. These data shed light on the molecular brakes involved in homeostatic macrophage polarization and suggest new therapeutic strategies to prevent inflammatory responses.
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影响因子：
4.4
作者：
Lee, Maggie M. K.;Chui, Ricky K. S.;Wong, Yung H.
通讯作者：
Wong, Yung H.
DOI：
10.4049/jimmunol.1202496
发表时间：
2013-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Banerjee S;Xie N;Cui H;Tan Z;Yang S;Icyuz M;Abraham E;Liu G
通讯作者：
Liu G
影响因子：
4.8
作者：
Bala, Shashi;Marcos, Miguel;Szabo, Gyongyi
通讯作者：
Szabo, Gyongyi
影响因子：
4.8
作者：
Banerjee, Sami;Cui, Huachun;Liu, Gang
通讯作者：
Liu, Gang
影响因子：
4.4
作者：
Aronoff, David M.;Hao, Yibai;Peters-Golden, Marc
通讯作者：
Peters-Golden, Marc