Relaxin induces matrix-metalloproteinases-9 and -13 via RXFP1: induction of MMP-9 involves the PI3K, ERK, Akt and PKC-ζ pathways.
Relaxin induces matrix-metalloproteinases-9 and -13 via RXFP1: induction of MMP-9 involves the PI3K, ERK, Akt and PKC-ζ pathways.
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DOI：
10.1016/j.mce.2012.07.006
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发表时间：
2012-11-05
影响因子：
4.1
通讯作者：
Kapila, Sunil
中科院分区：
文献类型：
--
作者：
Ahmad, Nisar;Wang, Wei;Nair, Remi;Kapila, Sunil
关键词：
我们确定了松弛素家族肽（RXFP）受体-1和-2在松弛素调节MMP-9和-13中的确切作用，并描绘了纤维软骨细胞中松弛素调节MMP-9的信号级联反应。松弛素处理的细胞，其中RXFP 1沉默导致松弛素诱导MMP-9和-13减少，而RXFP 1过表达增强松弛素诱导的这些蛋白酶的表达。抑制或过度表达RXFP 2导致松弛素诱导的MMP-9和-13没有变化。使用化学抑制剂和针对信号分子的siRNA的研究表明，PI 3 K、Akt、ERK和PKC-κ以及转录因子Elk-1、c-fos和较小程度的NF-κB参与松弛素对MMP-9的诱导。我们的研究结果提供了第一个特征的信号级联参与任何MMP松弛素的调节，并提供松弛素可能如何介导细胞外基质周转的机制的见解。
We determined the precise role of Relaxin Family Peptide (RXFP) receptors-1 and -2 in the regulation of MMP-9 and -13 by relaxin, and delineated the signaling cascade that contributes to relaxin’s modulation of MMP-9 in fibrocartilaginous cells. Relaxin treatment of cells in which RXFP1 was silenced resulted in diminished induction of MMP-9 and -13 by relaxin, whereas overexpression of RXFP1 potentiated the relaxin-induced expression of these proteinases. Suppression or overexpression of RXFP2 resulted in no changes in the relaxin-induced MMP-9 and -13. Studies using chemical inhibitors and siRNAs to signaling molecules showed that PI3K, Akt, ERK and PKC-ζ and the transcription factors Elk-1, c-fos and to a lesser extent NF-κB are involved in relaxin’s induction of MMP-9. Our findings provide the first characterization of signaling cascade involved in the regulation of any MMP by relaxin and offer mechanistic insights on how relaxin likely mediates extracellular matrix turnover.
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