MMP-12 regulates proliferation of mouse macrophages via the ERK/P38 MAPK pathways during inflammation
MMP-12 regulates proliferation of mouse macrophages via the ERK/P38 MAPK pathways during inflammation
复制标题
MMP-12 在炎症过程中通过 ERK/P38 MAPK 通路调节小鼠巨噬细胞的增殖
DOI：
10.1016/j.yexcr.2019.03.018
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发表时间：
2019-05-15
影响因子：
3.7
通讯作者：
Liao, Guiqing
中科院分区：
文献类型：
--
作者：
Guan, Chenyu;Xiao, Yudong;Liao, Guiqing
MMP-12是一种主要由巨噬细胞分泌并调节细胞外基质降解的金属蛋白酶（MMP）。MMP-12与肺气肿、心肌梗死、肝纤维化等多种疾病有关。然而，巨噬细胞中MMP-12与炎症相关的功能尚未得到充分研究。因此，本研究的目的是阐明MMP-12在小鼠巨噬细胞炎症过程中的作用。本研究通过流式细胞术显示，MMP-12与LPS暴露后小鼠肝脏中F4/80 +巨噬细胞的数量密切相关。qRT-PCR、流式细胞术、CCK-8、Western Blot和EdU染色分析显示，MMP-12敲低可调节RAW 264.7细胞系的促炎细胞因子和增殖。此外，下调MMP-12可降低P38和ERK1/2的表达和磷酸化水平。综上所述，这些数据表明MMP-12通过ERK/P38 MAPK信号通路促进小鼠巨噬细胞的增殖以及IL-1 β、IL-6、tnf - α、CXCL1和CXCL3的分泌。
MMP-12 is a metalloproteinase (MMP) mainly secreted by macrophages and regulating the degradation of the extracellular matrix. MMP-12 is related to several diseases such as emphysema, myocardial infarction and liver fibrosis. However, the functions associated with inflammation of MMP-12 in macrophages have not yet been fully investigated. Therefore, the aim of this study is to elucidate the role of MMP-12 in mouse macrophages during inflammation. Here we show by flow cytometry that MMP-12 was closely associated with the number of F4/80 + macrophages from mouse liver following exposure to LPS. Pro-inflammatory cytokines as well as the proliferation of RAW 264.7 cell line was modulated by MMP-12 knock down as illustrated by qRT-PCR, flow cytometry, CCK-8, Western Blot and EdU staining assays. Furthermore, down-regulation of MMP-12 decreased the expression and the phosphorylation levels of P38 and ERK1/2. Taken together, these data show that MMP-12 contributes to the proliferation of mouse macrophages as well as the secretion of IL-1 beta, IL-6, TNF-alpha, CXCL1 and CXCL3 through the ERK/P38 MAPK signaling pathway.