期刊
SCIENTIFIC REPORTS
卷 9, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-018-36917-9
关键词
-
资金
- Ministry of Education, Science and Culture of Japan [16K11279, 16H05484]
- Grants-in-Aid for Scientific Research [16H05484, 16K11279] Funding Source: KAKEN
The epithelial-mesenchymal transition (EMT) is a key process in fibrogenic diseases where transdifferentiated myofibroblasts produce excessive amounts of extracellular matrix, resulting in organ dysfunction. Idiopathic epiretinal membrane (iERM) is a vision-threatening disorder characterized by fibrocellular proliferation and contraction on the central retina. Muller glial cells, which regulate retinal physiology and structure, are the major cellular components in the iERM tissue; however, the pathological role of this cell type remains incompletely understood. Here we revealed the involvement of Muller glial-mesenchymal transition (GMT), as an alternative to EMT, in the pathogenesis of iERM lacking epithelial contribution in nature. Of various pro-fibrotic cytokines, transforming growth factor (TGF)-beta 1 stimulation to human Muller glial cells exclusively increased mRNA and protein levels of several EMT-related molecular markers, together with the transcription factor SNAIL but not SLUG or TWIST. TGF-beta 1-stimulated Muller cells also exhibited EMT-related cell motility, while reducing the expression of glutamine synthetase (GS), a Muller glial marker. Notably, all of these TGF-beta-induced EMT features were reversed by SNAI1 knockdown in Muller cells. iERM patient specimens demonstrated co-immunolocalization of SNAIL with TGF-beta 1, GS, and smooth muscle protein 22. Our data implicated a critical role of the TGF-beta-SNAIL axis in Muller GMT to promote iERM formation.
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