Role of adenosine monophosphate-activated protein kinase on cell migration, matrix contraction, and matrix metalloproteinase-1 and matrix metalloproteinase-2 production in nasal polyp-derived fibroblasts.

Abstract:

PURPOSE:Activation of adenosine monophosphate-activated protein kinase (AMPK) by metformin, as a master regulator of metabolism, is involved in airway tissue remodeling. Here, we investigated the physical role of AMPK on cell migration, matrix contraction, and the production of matrix metalloproteinases (MMP) in nasal polyp-derived fibroblasts (NPDF). METHODS:Primary NPDFs from six patients with chronic rhinosinusitis and nasal polyps were isolated and cultured. To assess the effect of AMPK on fibroblast migration, we conducted scratch and migration assays in NPDF treated with metformin and/or compound C. A collagen gel contraction assay measured activity of contractile. MMP expression was measured with reverse transcription-polymerase chain reaction, Western blot, and zymography. To evaluate for specific AMPK action, we examined by AMPK small interfering RNA. RESULTS:Metformin, an activator of AMPK, significantly inhibited cell migration in NPDFs in a dose-dependent manner. Compound C, an inhibitor of AMPK, partially reversed the inhibitory effect of metformin. Metformin also significantly decreased contractile activity, with a concomitant reduction in the production of MMP-1 and MMP-2 but not of MMP-9. Specific silencing that targeted AMPK resulted in the enhancement of mobility and contractility and in the production of MMP-1 and MMP-2. CONCLUSION:AMPK played an important role in regulating cell migration, matrix contraction, and MMP production in NPDFs, which provided data that AMPK activator might be a therapeutic target for the prevention of tissue remodeling in nasal polyps.

journal_name

Am J Rhinol Allergy

authors

Um JY,Lee SA,Park JH,Shin JM,Park IH,Lee HM

doi

10.2500/ajra.2017.31.4477

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

357-363

issue

6

eissn

1945-8924

issn

1945-8932

journal_volume

31

pub_type

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