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对羟基苯甲酸乙酯通过Wnt/β-连环蛋白信号通路诱导结膜下纤维化。

Ethylparaben induces subconjunctival fibrosis via the Wnt/β-catenin signaling pathway.

作者信息

Liu Fengge, Kong Xiangfeng, Kong Hui

机构信息

Department of Ophthalmology, Zoucheng People's Hospital, Zoucheng, Shandong 273500, P.R. China.

出版信息

Exp Ther Med. 2021 Apr;21(4):295. doi: 10.3892/etm.2021.9726. Epub 2021 Jan 28.

DOI:10.3892/etm.2021.9726
PMID:33717238
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7885073/
Abstract

The aim of the present study was to explore the etiology of subconjunctival fibrosis (SCF) induced by ethylparaben, the most prevalent preservative in Chinese eye drops. Ethylparaben was administered to the left eyes of male Sprague-Dawley rats in the experimental group twice daily for 1 month, whereas the control group received PBS. Experimental group rats displayed a mild promotion in density of fibroblasts and a tighter deposition of collagen in the bulbar subepithelial connective tissue compared with the control group. Furthermore, the present findings revealed that extracellular matrix expression was promoted in murine bulbar conjunctival tissues in the experimental group. In primary conjunctival fibroblasts, expression of ECM triggered by ethylparaben was suppressed by XAV-939. Furthermore, stimulation of the Wnt/β-catenin axis triggered by ethylparaben was impaired by XAV-939. In conclusion, SCF triggered by ethylparaben results from extra ECM generation of conjunctival fibroblasts via the Wnt/β-catenin axis.

摘要

本研究的目的是探究对羟基苯甲酸乙酯（中国滴眼液中最常见的防腐剂）诱导的结膜下纤维化（SCF）的病因。对实验组雄性Sprague-Dawley大鼠的左眼每日给药两次对羟基苯甲酸乙酯，持续1个月，而对照组接受磷酸盐缓冲液（PBS）。与对照组相比，实验组大鼠眼球结膜下结缔组织中的成纤维细胞密度轻度增加，胶原蛋白沉积更紧密。此外，本研究结果显示，实验组小鼠眼球结膜组织中的细胞外基质表达增加。在原代结膜成纤维细胞中，XAV-939可抑制对羟基苯甲酸乙酯触发的细胞外基质（ECM）表达。此外，XAV-939可削弱对羟基苯甲酸乙酯触发的Wnt/β-连环蛋白轴的激活。总之，对羟基苯甲酸乙酯引发的SCF是结膜成纤维细胞通过Wnt/β-连环蛋白轴产生额外细胞外基质所致。