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Aldosterone up-regulates MMP-9 and MMP-9/NGAL expression in human neutrophils through p38, ERK1/2 and PI3K pathways

Abstract : 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.
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https://hal.univ-lorraine.fr/hal-01481923
Contributor : Simpa Ul <>
Submitted on : Friday, March 3, 2017 - 9:30:40 AM
Last modification on : Friday, November 29, 2019 - 2:32:15 AM

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Alexandre Gilet, Feng Zou, Meriem Boumenir, Jean-Pol Frippiat, Simon N. Thornton, et al.. Aldosterone up-regulates MMP-9 and MMP-9/NGAL expression in human neutrophils through p38, ERK1/2 and PI3K pathways. Experimental Cell Research, Elsevier, 2015, 331 (1), pp.152 - 163. ⟨10.1016/j.yexcr.2014.11.004⟩. ⟨hal-01481923⟩

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