SNX10 Plays a Critical Role in MMP9 Secretion via JNK-p38-ERK Signaling Pathway
SNX10 Plays a Critical Role in MMP9 Secretion via JNK-p38-ERK Signaling Pathway
复制标题
SNX10 通过 JNK-p38-ERK 信号通路在 MMP9 分泌中发挥关键作用
DOI：
10.1002/jcb.26132
复制
发表时间：
2017-12-01
影响因子：
4
通讯作者：
Shen, Xiaoyan
中科院分区：
文献类型：
--
作者：
Zhou, Chun;Wang, Ying;Shen, Xiaoyan
基质金属蛋白酶（MMPs）在细胞外基质（ECM）的降解中起着关键作用。分选连接蛋白（SNX）10是SNX家族的成员，其功能是调节内体分选和破骨细胞活化，在类风湿性关节炎的骨侵蚀中起重要作用。本研究旨在探讨SNX 10对MMP 9分泌的影响及其可能机制。通过免疫染色和免疫共沉淀，我们发现SNX 10与MMP 9广泛共定位，表明SNX 10可能参与MMP 9的运输。通过SiRNA敲除SNX 10后，MMP 9的分泌和活性明显减少，但蛋白质含量增加。相反，SNX 10的过表达可增加分泌和活性水平。SNX 10的缺乏使破骨细胞的分化和骨吸收功能受损，MMP 9的活性较WT低。SNX 10基因敲除破骨细胞中JNK、p38和ERK磷酸化水平明显下调。我们的研究结果首次证实了SNX 10在MMP 9的运输和分泌中的作用，并为SNX 10作为骨破坏性疾病的可能治疗靶点提供了证据。J.细胞。118：4664-4671，2017. (c)2017 Wiley Periodicals，Inc.
Matrix metalloproteinases (MMPs) plays a critical role in the degradation of extracellular matrix (ECM). Sorting nexin (SNX) 10 is a member of the SNX family, which functions in regulation of endosomal sorting and osteoclast activation, has been implicated to play an important role in the bone erosion of rheumatoid arthritis. In this study, we aimed to investigate the possible role of SNX10 on MMP9 secretion and the potential mechanism. By immunostaining and co-immunoprecipitation, we found that SNX10 was extensively co-localized with MMP9, indicating that SNX10 might participate in MMP9 trafficking. After knocking down SNX10 via siRNA, the secretion and activity of MMP9 was significantly reduced, but the amount of protein was increased. By contraries, over-expression of SNX10 could increase the secretion and activity levels. Deficiency of SNX10 impaired the differentiation and bone resorption function of osteoclast, with a low activity of MMP9 compared to WT one. In SNX10 knockout osteoclast, the phosphorylation levels of JNK, p38, and ERK were obviously down-regulated. Our results first identified the role of SNX10 in MMP9 trafficking and secretion, and provided an evidence for SNX10 as a possible therapeutic target for bone destructing disease. J. Cell. Biochem. 118: 4664-4671, 2017. (c) 2017 Wiley Periodicals, Inc.