13-cis Retinoic Acid-Mediated Modulation of Human Meibomian Gland Epithelial Cells Development: Implications for In Vitro Modeling of Meibomian Gland Dysfunction.
{"title":"13-<i>cis</i> Retinoic Acid-Mediated Modulation of Human Meibomian Gland Epithelial Cells Development: Implications for <i>In Vitro</i> Modeling of Meibomian Gland Dysfunction.","authors":"Ning Wang, Kelan Yuan, Shuo Yang, Xiuming Jin","doi":"10.1089/jop.2024.0027","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Purpose:</i></b> This study aimed to investigate the effect of 13-<i>cis</i> retinoic acid (13-<i>cis</i> RA) on human meibomian gland epithelial cells (HMGECs) and explore the potential of using this experimental model as an <i>in vitro</i> approach for studying meibomian gland dysfunction (MGD). <b><i>Methods:</i></b> First, HMGECs were cultured with 13-<i>cis</i> 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 (<i>PPARγ</i>) antagonist GW9662 was used as a control to assess the impact of 13-<i>cis</i> RA on <i>PPARγ</i>. <b><i>Results:</i></b> 13-<i>cis</i> 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 <i>Ki67</i>, antioxidant <i>SOD-2</i>, and <i>Nrf-2</i>. However, the expression of the pro-inflammatory factors <i>IL-1β</i>, <i>IL-8</i>, <i>MMP9</i>, and oxidative stress markers <i>NOX-4</i> 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 (<i>ADFP4</i>), elongation of very long chain fatty acid protein 4 (<i>ELOVL4</i>), sterol regulatory element-binding protein 2 (<i>SREBP-2</i>), and <i>PPARγ</i>. <b><i>Conclusion:</i></b> 13-<i>cis</i> RA inhibited cell viability, promoted inflammation and oxidative stress, and suppressed meibum synthesis through the <i>PPARγ</i> pathway. Our study shed light on the effect of 13-<i>cis</i> RA on HMGECs and provided a promising direction for studying MGD <i>in vitro</i>.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Ocular Pharmacology and Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/jop.2024.0027","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.