LY2109761, Transforming Growth Factor β Receptor Type I and Type II Dual Inhibitor, is a Novel Approach to Suppress Endothelial Mesenchymal Transformation in Human Corneal Endothelial Cells

Author:

Zhang Zhi-hua,Miao Yu-yu,Ke Bi-lian,Liu Kun,Xu Xun

Abstract

Background/Aims: Preventing undesirable endothelial-mesenchymal transformation (EnMT) with repetitious in vitro expansion of human corneal endothelial cells (CECs) is a pivotal issue in cornea regeneration. Previous studies have shown that inhibition of the TGF-β pathway reduces epithelial-mesenchymal transformation. However, its potential role in EnMT remains poorly understood. As such, the effect of LY2109761, a novel TGF-β receptor type I and type II dual inhibitor, was investigated on EnMT. Methods: CECs cultured with various concentrations of LY2109761 were evaluated for their growth rate and phenotype. Additionally, the expression of functional markers (sodium-potassium pump Na+/K+-ATPase and the tight junction protein ZO-1) and mesenchymal markers (CD73, fibronectin, and vimentin) was detected using immunostaining and western blot. The mRNA expressions were also assayed by real-time polymerase chain reaction analysis. Results: At a 1 μM concentration, LY2109761 did not influence the proliferation of CECs and subsequent experiments were therefore performed using this concentration. Furthermore, CECs cultured in the presence of 1 μM LY2109761 maintained their ability to grow as a monolayer of hexagonal-shaped cells. The expression of functional markers increased in LY2109761-treated CECs, while the expression of mesenchymal markers decreased (both in protein and mRNA levels). Conclusion: Inhibition of TGF-β receptor type I and type II by LY2109761 maintained the phenotype of CECs and inhibited the EnMT process. These results indicate the possible continuous in vitro expansion of CECs with normal function.

Publisher

S. Karger AG

Subject

Physiology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3