Smurf1 通过 JNK 和 p38 MAPK 信号通路调节巨噬细胞的增殖、凋亡和迁移。
Smurf1 regulates macrophage proliferation, apoptosis and migration via JNK and p38 MAPK signaling pathways.
机构信息
Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Comparative Medical Center, Peking Union Medical College, Beijing, 100021, China; Department of Inorganic Non-metallic Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China.
Center for Drug Evaluation, China Food and Drug Administration, Beijing, 100038, China.
出版信息
Mol Immunol. 2018 May;97:20-26. doi: 10.1016/j.molimm.2018.03.005. Epub 2018 Mar 15.
Smad ubiquitylation regulatory factor 1 (Smurf1) has been identified to play a critical role in bone homeostasis, development, cell cycle regulation and tumorigenesis. However, the role of Smurf1 in macrophage proliferation, apoptosis and migration is still unclear. Here, we show that Smurf1 expression was elevated in LPS-induced RAW264.7 macrophage and mouse embryonic fibroblasts (MEFs). And we found that knockdown of Smurf1 suppresses macrophage proliferation but promotes apoptosis and migration. Furthermore, JNK and p38 MAPK signaling were upregulated in Smurf1-depleted cells. And inhibition of JNK and p38 MAPK signaling in Smurf1 knockdown cells rescue the phenotypes of macrophage proliferation, apoptosis and migration. Therefore, our study suggests that Smurf1 is a new positive regulator for macrophage proliferation and apoptosis, but a negative regulator for macrophage migration.
Smad 泛素连接酶调节因子 1（Smurf1）在骨稳态、发育、细胞周期调控和肿瘤发生中发挥着关键作用。然而，Smurf1 在巨噬细胞增殖、凋亡和迁移中的作用尚不清楚。在这里，我们发现 Smurf1 的表达在 LPS 诱导的 RAW264.7 巨噬细胞和小鼠胚胎成纤维细胞（MEFs）中升高。我们发现，Smurf1 的敲低抑制巨噬细胞增殖，但促进凋亡和迁移。此外，Smurf1 耗竭细胞中 JNK 和 p38 MAPK 信号通路被上调。在 Smurf1 敲低细胞中抑制 JNK 和 p38 MAPK 信号通路可挽救巨噬细胞增殖、凋亡和迁移的表型。因此，我们的研究表明 Smurf1 是巨噬细胞增殖和凋亡的新的正调控因子，但却是巨噬细胞迁移的负调控因子。
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