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Cigarette Smoke Extract Stimulates MMP-2 Production in Nasal Fibroblasts via ROS/PI3K, Akt, and NF-κB Signaling Pathways

Cigarette smoke exposure has been shown to be associated with chronic rhinosinusitis and tissue remodeling. The present study aimed to investigate the effects of cigarette smoke extract (CSE) on matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) production in nasal fibro...

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Autores principales: Park, Joo-Hoo, Shin, Jae-Min, Yang, Hyun-Woo, Kim, Tae Hoon, Lee, Seung Hoon, Lee, Heung-Man, Cho, Jae-Gu, Park, Il-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465436/
https://www.ncbi.nlm.nih.gov/pubmed/32806646
http://dx.doi.org/10.3390/antiox9080739
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author Park, Joo-Hoo
Shin, Jae-Min
Yang, Hyun-Woo
Kim, Tae Hoon
Lee, Seung Hoon
Lee, Heung-Man
Cho, Jae-Gu
Park, Il-Ho
author_facet Park, Joo-Hoo
Shin, Jae-Min
Yang, Hyun-Woo
Kim, Tae Hoon
Lee, Seung Hoon
Lee, Heung-Man
Cho, Jae-Gu
Park, Il-Ho
author_sort Park, Joo-Hoo
collection PubMed
description Cigarette smoke exposure has been shown to be associated with chronic rhinosinusitis and tissue remodeling. The present study aimed to investigate the effects of cigarette smoke extract (CSE) on matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) production in nasal fibroblasts and to determine the underlying molecular mechanisms. Primary nasal fibroblasts from six patients were isolated and cultured. After the exposure of fibroblasts to CSE, the expression levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured by real-time PCR, ELISA, and immunofluorescence staining. The enzymatic activities of MMP-2 and MMP-9 were measured by gelatin zymography. Reactive oxygen species (ROS) production was analyzed using dichloro-dihydro-fluorescein diacetate and Amplex Red assays. PI3K/Akt phosphorylation and NF-κB activation were determined by Western blotting and luciferase assay. CSE significantly increased MMP-2 expression and inhibited TIMP-2 expression but did not affect MMP-9 and TIMP-1 expression. Furthermore, CSE significantly induced ROS production. However, treatment with ROS scavengers, specific PI3K/Akt inhibitors, NF-κB inhibitor, and glucocorticosteroids significantly decreased MMP-2 expression and increased TIMP-2 expression. Our results suggest that steroids inhibit CSE-regulated MMP-2 and TIMP-2 production and activation through the ROS/ PI3K, Akt, and NF-κB signaling pathways in nasal fibroblasts. CSE may contribute to the pathogenesis of chronic rhinosinusitis by regulating MMP-2 and TIMP-2 expression.
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spelling pubmed-74654362020-09-04 Cigarette Smoke Extract Stimulates MMP-2 Production in Nasal Fibroblasts via ROS/PI3K, Akt, and NF-κB Signaling Pathways Park, Joo-Hoo Shin, Jae-Min Yang, Hyun-Woo Kim, Tae Hoon Lee, Seung Hoon Lee, Heung-Man Cho, Jae-Gu Park, Il-Ho Antioxidants (Basel) Article Cigarette smoke exposure has been shown to be associated with chronic rhinosinusitis and tissue remodeling. The present study aimed to investigate the effects of cigarette smoke extract (CSE) on matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) production in nasal fibroblasts and to determine the underlying molecular mechanisms. Primary nasal fibroblasts from six patients were isolated and cultured. After the exposure of fibroblasts to CSE, the expression levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured by real-time PCR, ELISA, and immunofluorescence staining. The enzymatic activities of MMP-2 and MMP-9 were measured by gelatin zymography. Reactive oxygen species (ROS) production was analyzed using dichloro-dihydro-fluorescein diacetate and Amplex Red assays. PI3K/Akt phosphorylation and NF-κB activation were determined by Western blotting and luciferase assay. CSE significantly increased MMP-2 expression and inhibited TIMP-2 expression but did not affect MMP-9 and TIMP-1 expression. Furthermore, CSE significantly induced ROS production. However, treatment with ROS scavengers, specific PI3K/Akt inhibitors, NF-κB inhibitor, and glucocorticosteroids significantly decreased MMP-2 expression and increased TIMP-2 expression. Our results suggest that steroids inhibit CSE-regulated MMP-2 and TIMP-2 production and activation through the ROS/ PI3K, Akt, and NF-κB signaling pathways in nasal fibroblasts. CSE may contribute to the pathogenesis of chronic rhinosinusitis by regulating MMP-2 and TIMP-2 expression. MDPI 2020-08-12 /pmc/articles/PMC7465436/ /pubmed/32806646 http://dx.doi.org/10.3390/antiox9080739 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Park, Joo-Hoo
Shin, Jae-Min
Yang, Hyun-Woo
Kim, Tae Hoon
Lee, Seung Hoon
Lee, Heung-Man
Cho, Jae-Gu
Park, Il-Ho
Cigarette Smoke Extract Stimulates MMP-2 Production in Nasal Fibroblasts via ROS/PI3K, Akt, and NF-κB Signaling Pathways
title Cigarette Smoke Extract Stimulates MMP-2 Production in Nasal Fibroblasts via ROS/PI3K, Akt, and NF-κB Signaling Pathways
title_full Cigarette Smoke Extract Stimulates MMP-2 Production in Nasal Fibroblasts via ROS/PI3K, Akt, and NF-κB Signaling Pathways
title_fullStr Cigarette Smoke Extract Stimulates MMP-2 Production in Nasal Fibroblasts via ROS/PI3K, Akt, and NF-κB Signaling Pathways
title_full_unstemmed Cigarette Smoke Extract Stimulates MMP-2 Production in Nasal Fibroblasts via ROS/PI3K, Akt, and NF-κB Signaling Pathways
title_short Cigarette Smoke Extract Stimulates MMP-2 Production in Nasal Fibroblasts via ROS/PI3K, Akt, and NF-κB Signaling Pathways
title_sort cigarette smoke extract stimulates mmp-2 production in nasal fibroblasts via ros/pi3k, akt, and nf-κb signaling pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465436/
https://www.ncbi.nlm.nih.gov/pubmed/32806646
http://dx.doi.org/10.3390/antiox9080739
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