FGF-1 reverts epithelial-mesenchymal transition induced by TGF-β1 through MAPK/ERK kinase pathway

Author:

Ramos Carlos1,Becerril Carina1,Montaño Martha1,García-De-Alba Carolina1,Ramírez Remedios2,Checa Marco1,Pardo Annie2,Selman Moisés1

Affiliation:

1. Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas and

2. Facultad de Ciencias, Universidad Nacional Autónoma de México, México City, México

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the expansion of the fibroblast/myofibroblast population and aberrant remodeling. However, the origin of mesenchymal cells in this disorder is still under debate. Recent evidence indicates that epithelial-mesenchymal transition (EMT) induced primarily by TGF-β1 plays an important role; however, studies regarding the opposite process, mesenchymal-epithelial transition, are scanty. We have previously shown that fibroblast growth factor-1 (FGF-1) inhibits several profibrogenic effects of TGF-β1. In this study, we examined the effects of FGF-1 on TGF-β1-induced EMT. A549 and RLE-6TN (human and rat) alveolar epithelial-like cell lines were stimulated with TGF-β1 for 72 h, and then, in the presence of TGF-β1, were cultured with FGF-1 plus heparin for an additional 48 h. After TGF-β1 treatment, epithelial cells acquired a spindle-like mesenchymal phenotype with a substantial reduction of E-cadherin and cytokeratins and concurrent induction of α-smooth muscle actin measured by real-time PCR, Western blotting, and immunocytochemistry. FGF-1 plus heparin reversed these morphological changes and returned the epithelial and mesenchymal markers to control levels. Signaling pathways analyzed by selective pharmacological inhibitors showed that TGF-β1 induces EMT through Smad pathway, while reversion by FGF-1 occurs through MAPK/ERK kinase pathway, resulting in ERK-1 phosphorylation and Smad2 dephosphorylation. These findings indicate that TGF-β1-induced EMT is reversed by FGF-1 and suggest therapeutic approaches to target this process in IPF.

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,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