MCPIP1 Regulates Fibroblast Migration in 3-D Collagen Matrices Downstream of MAP Kinases and NF-κB.
MCPIP1 Regulates Fibroblast Migration in 3-D Collagen Matrices Downstream of MAP Kinases and NF-κB.
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MCPIP1 调节 MAP 激酶和 NF-kappaB 下游 3-D 胶原基质中成纤维细胞的迁移。
DOI：
10.1038/jid.2015.334
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Carlson MA
中科院分区：
文献类型：
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作者：
Chao J;Dai X;Peña T;Doyle DA;Guenther TM;Carlson MA
成纤维细胞填充的3D胶原基质已被用于模拟基质收缩、细胞运动和一般成纤维细胞生物学。单核细胞趋化蛋白诱导蛋白1(MCPIP1)具有调节炎症、血管生成和细胞运动的作用。在本研究中，我们证明了MCPIP1的诱导作用是通过激活丝裂原活化蛋白激酶、磷酸肌醇3-激酶和核因子-κB来实现的。此外，MCPIP1的诱导还与抑制成纤维细胞从嵌套的胶原基质中迁移有关。MCPIP1的诱导或异位表达也上调了P53。P53的RNA干扰可阻止MCPIP1的诱导或异位表达所产生的迁移抑制。我们的发现提示MCPIP1作为分子开关在嵌套式胶原基质模型中调节成纤维细胞迁移的新作用。
The fibroblast-populated 3D collagen matrix has been used to model matrix contraction, cell motility, and general fibroblast biology. MCPIP1 (monocyte chemotactic protein-induced protein 1) has been shown to regulate inflammation, angiogenesis, and cellular motility. In the present study, we demonstrated induction of MCPIP1 in human fibroblasts embedded in the stress-released 3D collagen matrix, which occurred through activation of mitogen-activated protein kinases, phosphoinositide 3-kinase, and NF-κB. Furthermore, MCPIP1 induction was associated with inhibition of fibroblast migration out of the nested collagen matrix. MCPIP1 induction or ectopic expression also upregulated p53. RNA interference of p53 prevented the inhibition of migration produced by induction or ectopic expression of MCPIP1. Our findings suggest a new role for MCPIP1 as a molecular switch that regulates fibroblast migration in the nested collagen matrix model.