通过阻断具有 PDZ 结合基元活性的是相关蛋白/转录辅激活因子,抑制成人视网膜色素上皮-19 细胞中结缔组织生长因子的表达。

IF 1.9 4区 医学 Q2 OPHTHALMOLOGY Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-05-01 Epub Date: 2024-03-22 DOI:10.1089/jop.2023.0141
Yoko Murakami, Toshiyasu Imaizumi, Kouhei Hashizume, Yu Tezuka, Yusuke Oku, Naoyuki Nishiya, Atsushi Sanbe, Daijiro Kurosaka
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引用次数: 0

摘要

目的:研究是相关蛋白(YAP)和具有 PDZ 结合基调的转录辅激活因子(TAZ)对成人视网膜色素上皮(ARPE)-19 细胞中结缔组织生长因子(CTGF)表达的影响。我们还研究了新型泛转录增强关联域(TEAD)抑制剂 K-975 和植物黄酮类化合物木犀草素对 CTGF 表达的抑制作用。研究方法用YAP或TAZ过表达质粒转染ARPE-19细胞,或用转化生长因子(TGF)-β2处理ARPE-19细胞。使用或不使用 K-975 或叶黄素培养细胞。使用实时 PCR 检测 YAP、TAZ 和 CTGF 的表达。结果显示过表达 YAP 或 TAZ 的 ARPE-19 细胞的 CTGF 表达明显增加。K-975 或单用木犀草素可减轻这种增加。TGF-β2 处理不仅能显著提高 YAP 和 TAZ 的表达,还能显著提高 CTGF 在 ARPE-19 细胞中的表达。加入 K-975 或叶黄素后,TGF-β2 处理增强的 CTGF 表达量大大降低。结论过表达 YAP 或 TAZ 以及 TGF-β2 处理会导致 ARPE-19 细胞中 CTGF 的表达增加。用 K-975 和叶黄素处理可减轻这些增加。这些研究结果表明,YAP和TAZ可能与ARPE-19细胞中CTGF的表达有关,K-975和木犀草素可作为潜在的治疗药物,用于防止玻璃体视网膜纤维化中CTGF的产生。
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Inhibition of Connective Tissue Growth Factor Expression in Adult Retinal Pigment Epithelial-19 Cells by Blocking Yes-Associated Protein/Transcriptional Coactivator with PDZ-Binding Motif Activity.

Purpose: To investigate the effect of yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) on connective tissue growth factor (CTGF) expression in adult retinal pigment epithelial (ARPE)-19 cells. We also studied the inhibitory effect of K-975, a new pan-transcriptional enhanced associate domain (TEAD) inhibitor, and luteolin, a plant-derived flavonoid on CTGF expression. Methods: ARPE-19 cells were transfected with either YAP or TAZ overexpression plasmid or treated with transforming growth factor (TGF)-β2. The cells were cultured either with or without K-975 or luteolin. The expression of YAP, TAZ, and CTGF was examined using real-time PCR. Results: ARPE-19 cells overexpressing YAP or TAZ exhibited significantly increased CTGF expression. This increase was attenuated by K-975 or luteolin alone. TGF-β2 treatment significantly raised the expression of not just YAP and TAZ, but also CTGF in ARPE-19 cells. TGF-β2 treatment-enhanced CTGF expression was considerably lowered by the addition of K-975 or luteolin. Conclusions: Overexpression of YAP or TAZ and treatment with TGF-β2 led to an increase in the expression of CTGF in ARPE-19 cells. These increases were attenuated by treatment with K-975 and luteolin. These findings suggest that YAP and TAZ may be related to the expression of CTGF in ARPE-19 cells and that K-975 and luteolin can be explored as potential therapeutic agents for preventing CTGF production in vitreoretinal fibrosis.

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来源期刊
CiteScore
4.60
自引率
4.30%
发文量
72
审稿时长
1 months
期刊介绍: Journal of Ocular Pharmacology and Therapeutics is the only peer-reviewed journal that combines the fields of ophthalmology and pharmacology to enable optimal treatment and prevention of ocular diseases and disorders. The Journal delivers the latest discoveries in the pharmacokinetics and pharmacodynamics of therapeutics for the treatment of ophthalmic disorders. Journal of Ocular Pharmacology and Therapeutics coverage includes: Glaucoma Cataracts Retinal degeneration Ocular infection, trauma, and toxicology Ocular drug delivery and biotransformation Ocular pharmacotherapy/clinical trials Ocular inflammatory and immune disorders Gene and cell-based therapies Ocular metabolic disorders Ocular ischemia and blood flow Proliferative disorders of the eye Eyes on Drug Discovery - written by Gary D. Novack, PhD, featuring the latest updates on drug and device pipeline developments as well as policy/regulatory changes by the FDA.
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