Abstract:
: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 G0̸G1 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 PI3K̸AKT signaling pathway.
journal_name
Int J Mol Medjournal_title
International journal of molecular medicineauthors
Sun L,Dong Y,Zhao J,Yin Y,Tong B,Zheng Y,Xin Hdoi
10.3892/ijmm.2017.3323subject
Has Abstractpub_date
2018-03-01 00:00:00pages
1331-1338issue
3eissn
1107-3756issn
1791-244Xjournal_volume
41pub_type
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