Aldosterone up-regulates MMP-9 and MMP-9/NGAL expression in human neutrophils through p38, ERK1/2 and PI3K pathways
Aldosterone up-regulates MMP-9 and MMP-9/NGAL expression in human neutrophils through p38, ERK1/2 and PI3K pathways
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DOI：
10.1016/j.yexcr.2014.11.004
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发表时间：
2015-02-01
影响因子：
3.7
通讯作者：
Ropars, Armelle
中科院分区：
文献类型：
--
作者：
Gilet, Alexandre;Zou, Feng;Ropars, Armelle
醛固酮和盐皮质激素受体是重要的炎症调节因子。在此过程中，趋化因子和基质金属蛋白酶（如MMP-9）降解细胞外基质，帮助白细胞迅速到达并浸润损伤组织，这是组织修复所必需的两个过程。白细胞，如中性粒细胞，是MMP-9的丰富来源，并具有盐皮质激素受体（MR）。本研究的目的是探讨醛固酮是否能够调节人中性粒细胞中的proMMP-9、活性MMP-9和MMP-9/NGAL的产生。在这里，我们表明，醛固酮增加MMP-9 mRNA的剂量和时间依赖性的方式。该激素还剂量依赖性地上调proMMP-9和活性MMP-9蛋白的释放以及MMP-9/NGAL蛋白复合物。PI 3 K，p38和ERK 1/2抑制减少这些醛固酮诱导的中性粒细胞的产生。此外，螺内酯，一种MR拮抗剂，抵消醛固酮诱导的proMMP-9，活性MMP-9和MMP-9/NGAL复合物的增加。这些发现表明，醛固酮可以通过调节中性粒细胞活性和促进细胞外基质降解来参与组织修复。(C)2014爱思唯尔公司All rights reserved.
Aldosterone and mineralocorticoid receptors are important regulators of inflammation. During this process, chemokines and extracellular matrix degradation by matrix metalloproteases, such as MMP-9, help leukocytes reaching swiftly and infiltrating the injured tissue, two processes essential for tissue repair. Leukocytes, such as neutrophils, are a rich source of MMP-9 and possess mineralocorticoid receptors (MR). The aim of our study was to investigate whether aldosterone was able to regulate proMMP-9, active MMP-9 and MMP-9/NGAL production in human neutrophils. Here we show that aldosterone increased MMP-9 mRNA in a dose- and time-dependent manner. This hormone up-regulated also dose-dependently proMMP-9 and active MMP-9 protein release as well as the MMP-9/NGAL protein complex. PI3K, p38 and ERK1/2 inhibition diminished these aldosterone-induced neutrophil productions. Furthermore, spironolactone, a MR antagonist, counteracted aldosterone-induced increases of proMMP-9, active MMP-9 and MMP-9/NGAL complex. These findings indicate that aldosterone could participate in tissue repair by modulating neutrophil activity and favoring extracellular matrix degradation. (C) 2014 Elsevier Inc. All rights reserved.