Cargando…

NPPB modulates apoptosis, proliferation, migration and extracellular matrix synthesis of conjunctival fibroblasts by inhibiting PI3K/AKT signaling

When treating glaucoma, excessive scar tissue reactions reduce the postoperative survival rate of the filtering bleb. Accumulating evidence has demonstrated that the proliferation, migration and extracellular matrix (ECM) synthesis of fibroblasts are important molecular mechanisms underlying scar fo...

Descripción completa

Detalles Bibliográficos
Autores principales: Sun, Lixia, Dong, Yaru, Zhao, Jing, Yin, Yuan, Tong, Bainan, Zheng, Yajuan, Xin, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819927/
https://www.ncbi.nlm.nih.gov/pubmed/29286070
http://dx.doi.org/10.3892/ijmm.2017.3323
_version_ 1783301290073260032
author Sun, Lixia
Dong, Yaru
Zhao, Jing
Yin, Yuan
Tong, Bainan
Zheng, Yajuan
Xin, Hua
author_facet Sun, Lixia
Dong, Yaru
Zhao, Jing
Yin, Yuan
Tong, Bainan
Zheng, Yajuan
Xin, Hua
author_sort Sun, Lixia
collection PubMed
description When treating glaucoma, excessive scar tissue reactions reduce the postoperative survival rate of the filtering bleb. Accumulating evidence has demonstrated that the proliferation, migration and extracellular matrix (ECM) synthesis of fibroblasts are important molecular mechanisms underlying scar formation. Recent evidence has demonstrated that chloride channels play an important role in controlling cell proliferation, apoptosis, migration and the cell cycle process in several cell types, but the effects of chloride channels on conjunctival fibroblasts have not be studied. The aim of the present study was to investigate the effects of the chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) on cell proliferation, apoptosis, migration, cell cycle progression and ECM synthesis in human conjunctival fibroblasts (HConFs), and to further investigate the mechanism of resistance to scar formation following glaucoma filtration surgery. HConFs were exposed to NPPB or lubiprostone. Cell proliferation and viability was evaluated using the Cell Counting Kit-8. Cell migration was measured using Transwell migration and scratch-wound assays. Flow cytometry was used to study apoptosis and cell cycle progression. Quantitative polymerase chain reaction and western blot analyses were performed to determine mRNA and protein expression levels, respectively. Following NPPB treatment, HConFs exhibited reduced proliferation and migration, along with increased apoptosis. NPPB also inhibited cell cycle progression by arresting cells in the G0/G1 phase and reducing collagen I and fibronectin expression, as well as the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT). However, lubiprostone treatment exerted the opposite effects on HConFs. Therefore, NPPB treatment inhibited proliferation, migration, cell cycle progression and synthesis of the ECM, while promoting apoptosis in HConFs, by inhibiting the PI3K/AKT signaling pathway.
format Online
Article
Text
id pubmed-5819927
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-58199272018-03-02 NPPB modulates apoptosis, proliferation, migration and extracellular matrix synthesis of conjunctival fibroblasts by inhibiting PI3K/AKT signaling Sun, Lixia Dong, Yaru Zhao, Jing Yin, Yuan Tong, Bainan Zheng, Yajuan Xin, Hua Int J Mol Med Articles When treating glaucoma, excessive scar tissue reactions reduce the postoperative survival rate of the filtering bleb. Accumulating evidence has demonstrated that the proliferation, migration and extracellular matrix (ECM) synthesis of fibroblasts are important molecular mechanisms underlying scar formation. Recent evidence has demonstrated that chloride channels play an important role in controlling cell proliferation, apoptosis, migration and the cell cycle process in several cell types, but the effects of chloride channels on conjunctival fibroblasts have not be studied. The aim of the present study was to investigate the effects of the chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) on cell proliferation, apoptosis, migration, cell cycle progression and ECM synthesis in human conjunctival fibroblasts (HConFs), and to further investigate the mechanism of resistance to scar formation following glaucoma filtration surgery. HConFs were exposed to NPPB or lubiprostone. Cell proliferation and viability was evaluated using the Cell Counting Kit-8. Cell migration was measured using Transwell migration and scratch-wound assays. Flow cytometry was used to study apoptosis and cell cycle progression. Quantitative polymerase chain reaction and western blot analyses were performed to determine mRNA and protein expression levels, respectively. Following NPPB treatment, HConFs exhibited reduced proliferation and migration, along with increased apoptosis. NPPB also inhibited cell cycle progression by arresting cells in the G0/G1 phase and reducing collagen I and fibronectin expression, as well as the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT). However, lubiprostone treatment exerted the opposite effects on HConFs. Therefore, NPPB treatment inhibited proliferation, migration, cell cycle progression and synthesis of the ECM, while promoting apoptosis in HConFs, by inhibiting the PI3K/AKT signaling pathway. D.A. Spandidos 2018-03 2017-12-15 /pmc/articles/PMC5819927/ /pubmed/29286070 http://dx.doi.org/10.3892/ijmm.2017.3323 Text en Copyright: © Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Sun, Lixia
Dong, Yaru
Zhao, Jing
Yin, Yuan
Tong, Bainan
Zheng, Yajuan
Xin, Hua
NPPB modulates apoptosis, proliferation, migration and extracellular matrix synthesis of conjunctival fibroblasts by inhibiting PI3K/AKT signaling
title NPPB modulates apoptosis, proliferation, migration and extracellular matrix synthesis of conjunctival fibroblasts by inhibiting PI3K/AKT signaling
title_full NPPB modulates apoptosis, proliferation, migration and extracellular matrix synthesis of conjunctival fibroblasts by inhibiting PI3K/AKT signaling
title_fullStr NPPB modulates apoptosis, proliferation, migration and extracellular matrix synthesis of conjunctival fibroblasts by inhibiting PI3K/AKT signaling
title_full_unstemmed NPPB modulates apoptosis, proliferation, migration and extracellular matrix synthesis of conjunctival fibroblasts by inhibiting PI3K/AKT signaling
title_short NPPB modulates apoptosis, proliferation, migration and extracellular matrix synthesis of conjunctival fibroblasts by inhibiting PI3K/AKT signaling
title_sort nppb modulates apoptosis, proliferation, migration and extracellular matrix synthesis of conjunctival fibroblasts by inhibiting pi3k/akt signaling
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819927/
https://www.ncbi.nlm.nih.gov/pubmed/29286070
http://dx.doi.org/10.3892/ijmm.2017.3323
work_keys_str_mv AT sunlixia nppbmodulatesapoptosisproliferationmigrationandextracellularmatrixsynthesisofconjunctivalfibroblastsbyinhibitingpi3kaktsignaling
AT dongyaru nppbmodulatesapoptosisproliferationmigrationandextracellularmatrixsynthesisofconjunctivalfibroblastsbyinhibitingpi3kaktsignaling
AT zhaojing nppbmodulatesapoptosisproliferationmigrationandextracellularmatrixsynthesisofconjunctivalfibroblastsbyinhibitingpi3kaktsignaling
AT yinyuan nppbmodulatesapoptosisproliferationmigrationandextracellularmatrixsynthesisofconjunctivalfibroblastsbyinhibitingpi3kaktsignaling
AT tongbainan nppbmodulatesapoptosisproliferationmigrationandextracellularmatrixsynthesisofconjunctivalfibroblastsbyinhibitingpi3kaktsignaling
AT zhengyajuan nppbmodulatesapoptosisproliferationmigrationandextracellularmatrixsynthesisofconjunctivalfibroblastsbyinhibitingpi3kaktsignaling
AT xinhua nppbmodulatesapoptosisproliferationmigrationandextracellularmatrixsynthesisofconjunctivalfibroblastsbyinhibitingpi3kaktsignaling