前列腺素 E2 和 F2α 改变人睑板腺上皮细胞产生的选择性胆固醇酯和三酰甘油的表达。

Prostaglandin E2 and F2α Alter Expression of Select Cholesteryl Esters and Triacylglycerols Produced by Human Meibomian Gland Epithelial Cells.

机构信息

Department of Optometry and Vision Science, School of Optometry, University of Alabama at Birmingham, Birmingham, AL; and.

Department of Pharmacology and Toxicology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL.

出版信息

Cornea. 2022 Jan 1;41(1):95-105. doi: 10.1097/ICO.0000000000002835.

DOI:10.1097/ICO.0000000000002835

PMID:34483274

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8648972/

Abstract

PURPOSE

PGF2α analogs are commonly used to treat glaucoma and are associated with higher rates of meibomian gland dysfunction (MGD). The purpose of this study was to evaluate the physiological effects of PGF2α and PGE2 on immortalized human meibomian gland epithelial cells (HMGECs).

METHODS

HMGECs were immunostained for the 4 PGE2 receptors (EP1, EP2, EP3, and EP4) and 1 PGF2α receptor (FP) and imaged. Rosiglitazone-differentiated HMGECs were exposed to PGF2α and PGE2 (10-9 to 10-6 M) for 3 hours. Cell viability was assessed by an adenosine triphosphate-based luminescent assay, and lipid extracts were analyzed for cholesteryl esters (CEs), wax esters (WEs), and triacylglycerols (TAGs) by ESI-MSMSALL in positive ion mode by a Triple TOF 5600 Mass Spectrometer using SCIEX LipidView 1.3.

RESULTS

HMGECs expressed 3 PGE2 receptors (EP1, EP2, and EP4) and the 1 PGF2α receptor (FP). Neither PGE2 nor PGF2α showed signs of cytotoxicity at any of the concentrations tested. WEs were not detected from any of the samples, but both CEs and TAGs exhibited a diverse and dynamic profile. PGE2 suppressed select CEs (CE 22:1, CE 26:0, CE 28:1, and CE 30:1). PGF2α dose dependently increased several CEs (CE 20:2, CE 20:1, CE 22:1, and CE 24:0) yet decreased others. Both prostaglandins led to nonspecific TAG remodeling.

CONCLUSIONS

PGE2 and PGF2α showed minimal effect on HMGEC viability. PGF2α influences lipid expression greater than PGE2 and may do so by interfering with meibocyte differentiation. This work may provide insight into the mechanism of MGD development in patients with glaucoma treated with PGF2α analogs.

摘要

目的

PGF2α 类似物通常用于治疗青光眼，并且与更高的睑板腺功能障碍（MGD）发生率相关。本研究的目的是评估 PGF2α 和 PGE2 对永生化人睑板腺上皮细胞（HMGEC）的生理影响。

方法

对 HMGEC 进行 4 种 PGE2 受体（EP1、EP2、EP3 和 EP4）和 1 种 PGF2α 受体（FP）的免疫染色，并进行成像。用罗格列酮分化的 HMGEC 暴露于 PGF2α 和 PGE2（10-9 至 10-6 M）3 小时。通过三磷酸腺苷（ATP）基础发光测定法评估细胞活力，通过电喷雾串联质谱法（ESI-MSMSALL）在正离子模式下，使用三重四极杆 5600 质谱仪和 SCIEX LipidView 1.3 分析胆固醇酯（CEs）、蜡酯（WEs）和三酰基甘油（TAGs）的脂质提取物。

结果

HMGEC 表达 3 种 PGE2 受体（EP1、EP2 和 EP4）和 1 种 PGF2α 受体（FP）。在测试的任何浓度下，PGE2 和 PGF2α 均未显示出细胞毒性迹象。未从任何样品中检测到 WEs，但 CEs 和 TAGs 均表现出多样化和动态的特征。PGE2 抑制了几种 CE（CE 22:1、CE 26:0、CE 28:1 和 CE 30:1）。PGF2α 剂量依赖性地增加了几种 CE（CE 20:2、CE 20:1、CE 22:1 和 CE 24:0），但同时也降低了其他 CE。两种前列腺素均导致非特异性 TAG 重塑。