13-cis Retinoic Acid-Mediated Modulation of Human Meibomian Gland Epithelial Cells Development: Implications for In Vitro Modeling of Meibomian Gland Dysfunction.

IF 1.9 4区 医学 Q2 OPHTHALMOLOGY
Ning Wang, Kelan Yuan, Shuo Yang, Xiuming Jin
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Abstract

Purpose: This study aimed to investigate the effect of 13-cis retinoic acid (13-cis RA) on human meibomian gland epithelial cells (HMGECs) and explore the potential of using this experimental model as an in vitro approach for studying meibomian gland dysfunction (MGD). Methods: First, HMGECs were cultured with 13-cis RA at different doses and times, and cell viability and proliferation rates were assessed to determine the appropriate stimulation concentration and time. Subsequently, during the proliferation stage, the expression of proliferation, inflammation, and oxidative stress genes and their products were evaluated. The meibum synthesis capacity was determined during the differentiation stage. Additionally, the peroxisome proliferator-activated receptor gamma (PPARγ) antagonist GW9662 was used as a control to assess the impact of 13-cis RA on PPARγ. Results: 13-cis RA significantly inhibited cell viability and proliferation in a time-dose response manner. Under the stimulation of 2 and 5 μM for 48 h during the proliferation stage, a significant decrease was observed in the expression of cell proliferation markers Ki67, antioxidant SOD-2, and Nrf-2. However, the expression of the pro-inflammatory factors IL-1β, IL-8, MMP9, and oxidative stress markers NOX-4 and reactive oxygen species increased. During the differentiation stage, it suppressed meibum synthesis and the expression of meibocyte differentiation-related proteins adipose differentiation-associated protein 4 (ADFP4), elongation of very long chain fatty acid protein 4 (ELOVL4), sterol regulatory element-binding protein 2 (SREBP-2), and PPARγ. Conclusion: 13-cis RA inhibited cell viability, promoted inflammation and oxidative stress, and suppressed meibum synthesis through the PPARγ pathway. Our study shed light on the effect of 13-cis RA on HMGECs and provided a promising direction for studying MGD in vitro.

13-顺式维甲酸介导的人类睑板腺上皮细胞发育调控:睑板腺功能障碍体外模型的意义
目的:本研究旨在探讨 13-顺式维甲酸(13-cis RA)对人睑板腺上皮细胞(HMGECs)的影响,并探索将该实验模型作为研究睑板腺功能障碍(MGD)体外方法的潜力。研究方法首先,用不同剂量和时间的13-顺式RA培养HMGECs,评估细胞活力和增殖率,以确定合适的刺激浓度和时间。然后,在增殖阶段,评估增殖、炎症和氧化应激基因及其产物的表达。在分化阶段,测定了meibum的合成能力。此外,还使用过氧化物酶体增殖激活受体γ(PPARγ)拮抗剂 GW9662 作为对照,以评估 13-cis RA 对 PPARγ 的影响。结果13-顺式RA以时间剂量反应方式明显抑制细胞活力和增殖。在增殖期,2 μM和5 μM刺激48小时后,细胞增殖标志物Ki67、抗氧化剂SOD-2和Nrf-2的表达明显下降。然而,促炎因子 IL-1β、IL-8、MMP9 以及氧化应激标志物 NOX-4 和活性氧的表达却增加了。在分化阶段,它抑制了meibum的合成以及meibocyte分化相关蛋白脂肪分化相关蛋白4(ADFP4)、超长链脂肪酸伸长蛋白4(ELOVL4)、甾醇调节元件结合蛋白2(SREBP-2)和PPARγ的表达。结论:13-顺式 RA 通过 PPARγ 途径抑制细胞活力、促进炎症和氧化应激反应并抑制睑板腺分泌。我们的研究揭示了 13-cis RA 对 HMGECs 的影响,为在体外研究 MGD 提供了一个很好的方向。
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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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