دورية أكاديمية
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Antifibrotic role of low-dose mitomycin-c-induced cellular senescence in trabeculectomy models.

التفاصيل البيبلوغرافية
العنوان: Antifibrotic role of low-dose mitomycin-c-induced cellular senescence in trabeculectomy models.
المؤلفون: Le-Tien Lin, Jiann-Torng Chen, Da-Wen Lu, Ming-Cheng Tai, Chang-Min Liang, Ching-Long Chen, Shu-I Pao, Chih-Kang Hsu, Yi-Hao Chen
المصدر: PLoS ONE, Vol 15, Iss 6, p e0234706 (2020)
بيانات النشر: Public Library of Science (PLoS), 2020.
سنة النشر: 2020
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: PurposeWe assessed whether mitomycin-C (MMC) has different antifibrotic mechanisms in trabeculectomy wound healing.MethodsWe identified 2 concentrations of MMC as "low-dose" by using WST-1 assay, Lactic dehydrogenase assay, and fluorescence-activated cell sorting flow cytometry. Senescence-associated β-galactosidase (SA-β-gal) and fibrotic gene expression was examined through immunocytochemistry, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, Western blotting, zymography, and modified scratch assay in vitro. In vivo, 0.1 mL of MMC or normal saline was injected to Tenon's capsule before trabeculectomy in a rabbit model. SA-β-gal expression, apoptotic cell death, and collagen deposition in sites treated and not treated with MMC were evaluated using terminal dUTP nick end labeling assay and histochemical staining. Bleb function and intraocular pressure (IOP) levels were examined 3, 7, 14, 21, 28, and 35 days after trabeculectomy.ResultsIn vitro, human Tenon's fibroblast (HTF) senescence was confirmed by observing cell morphologic change, SA-β-gal accumulation, formation of senescence-associated heterochromatin, increased p16INK4a and p21CIP1/WAF1 expression, lower percentage of Ki-67-positive cells, and decreased COL1A1 release. Increased expression of α-SMA, COL1A1, and Smad2 signaling in TGF-β1-induced stress fibers were passivated in senescent HTFs. In addition, cellular migration enhanced by TGF-β1was inactivated. In vivo, histological examination indicated increased SA-β-gal accumulation, lower apoptosis ratios, and looser collagen deposition in sites treated with 0.2 μM MMC. Low-dose MMC-induced cellular senescence prolonged trabeculectomy bleb survival and reduced IOP levels in a rabbit model.ConclusionLow-dose MMC-induced cellular senescence is involved in the antifibrotic mechanism of trabeculectomy wound healing.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
32841345
Relation: https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0234706
URL الوصول: https://doaj.org/article/328413451d1e4c64b2a3e7aa87069c67
رقم الأكسشن: edsdoj.328413451d1e4c64b2a3e7aa87069c67
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
32841345
DOI:10.1371/journal.pone.0234706