MiR27a Promotes the Development of Macrophage-like Characteristics in 3T3-L1 Preadipocytes.
MiR27a Promotes the Development of Macrophage-like Characteristics in 3T3-L1 Preadipocytes.
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DOI：
10.7150/ijbs.26274
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发表时间：
2018
影响因子：
9.2
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Zhang M;Sheng S;Zhang W;Zhang J;Zhang Z;Zhang M;Hatch GM;Chen L
脂肪组织中经典激活的巨噬细胞(M1)的募集和极化有助于肥胖症的慢性低度炎症。脂肪组织前体细胞具有发展巨噬细胞样特征的能力，脂肪细胞来源的miR27a被认为促进体细胞的重编程。目前尚不清楚外源添加miR27a是否促进脂肪前体细胞的巨噬细胞样特性的发展。我们检测了转染miR27a模拟物的3T3-L1前脂肪细胞的巨噬细胞表面抗原、吞噬功能和迁移能力。与对照组相比，用miR27a模拟物转染3T3-L1前脂肪细胞可增加吞噬和迁移，并增加表达巨噬细胞标志物F4/80和MHC的细胞数量。M2和CD206巨噬细胞标志物未见改变。此外，与对照组相比，3T3-L1前脂肪细胞转染miR27a可模拟PPARγ的表达，激活NF-κB，促进炎性细胞因子MCP-1、α和IL-1β的分泌。抗炎因子Arg-1、IL-10、YM1、Fizz1水平无明显变化。在棕榈酸处理的分化3T3-L1脂肪细胞的条件培养液中，miR27a的分泌比对照组增加。与对照组相比，用该条件培养液培养3T3-L1前脂肪细胞可增加吞噬和迁移能力。最后，与对照组相比，将miR27a抑制剂转染分化的3T3-L1脂肪细胞制备的条件培养液减少了3T3-L1前脂肪细胞的吞噬和迁移。结果表明，PPARγ激动剂可逆转由miR27a过表达介导的NF-κB通路的激活，减少脂肪前体细胞的吞噬和迁移。此外，miR27a可能促进3T3-L1前脂肪细胞巨噬细胞样特性的形成。
Recruitment and polarization of classically activated (M1) macrophages within adipose tissue contribute to chronic low-grade inflammation in obesity. Adipose tissue precursor cells exhibit the capacity to develop macrophage-like characteristics and adipocyte-derived miR27a is known to promote reprogramming of somatic cells. It was unknown whether exogenous addition of miR27a promote the development of macrophage-like characteristics of adipose precursor cells. We examined macrophage surface antigen, phagocytosis and migration ability in 3T3-L1 preadipocytes transfected with miR27a mimics. Transfection of 3T3-L1 preadipocytes with miR27a mimics increased phagocytosis and migration and increased the number of cells expressing the macrophage makers F4/80 and MHC compared to controls. M2 and CD206 macrophage markers were unaltered. In addition, transfection of 3T3-L1 preadipocytes with miR27a mimics reduced PPARγ expression, activated NF-κB and promoted secretion of the inflammatory cytokines MCP-1, TNF-α and IL-1β compared to controls. The level of anti-inflammatory factors Arg-1, IL-10, Ym1 and Fizz1 were unaltered. Secretion of miR27a was increased in conditioned medium prepared from palmitic acid-treated differentiated 3T3-L1 adipocytes compared to controls. Incubation of 3T3-L1 preadipocytes with this conditioned medium increased phagocytosis and migration compared to controls. Finally, conditioned medium prepared from differentiated 3T3-L1 adipocytes transfection with miR27a inhibitors reduced phagocytosis and migration in 3T3-L1 preadipocytes compared to controls. The data indicate that PPARγ agonists may reverse the activation of NF-κB pathway mediated by miR27a overexpression and reduce phagocytosis and migration of adipose precursor cells. In addition, miR27a may promote the development of macrophage-like characteristics in 3T3-L1 preadipocytes.
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