Related Experiment Video
Updated: Jun 18, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
Tumor necrosis factor-alpha regulates transforming growth factor-beta-dependent epithelial-mesenchymal transition by
Eri Takahashi1, Osamu Nagano2, Takatsugu Ishimoto3
1From the Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo 160-8582; the Department of Ophthalmology and Visual Science, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556.
Abstract:
Aberrant epithelial-mesenchymal transition (EMT) is involved in development of fibrotic disorders and cancer invasion. Alterations of cell-extracellular matrix interaction also contribute to those pathological conditions. However, the functional interplay between EMT and cell-extracellular matrix interactions remains poorly understood. We now show that the inflammatory mediator tumor necrosis factor-alpha (TNF-alpha) induces the formation of fibrotic foci by cultured retinal pigment epithelial cells through activation of transforming growth factor-beta (TGF-beta) signaling in a manner dependent on hyaluronan-CD44-moesin interaction. TNF-alpha promoted CD44 expression and moesin phosphorylation by protein kinase C, leading to the pericellular interaction of hyaluronan and CD44. Formation of the hyaluronan-CD44-moesin complex resulted in both cell-cell dissociation and increased cellular motility through actin remodeling. Furthermore, this complex was found to be associated with TGF-beta receptor II and clathrin at actin microdomains, leading to activation of TGF-beta signaling. We established an in vivo model of TNF-alpha-induced fibrosis in the mouse eye, and such ocular fibrosis was attenuated in CD44-null mice. The production of hyaluronan and its interaction with CD44, thus, play an essential role in TNF-alpha-induced EMT and are potential therapeutic targets in fibrotic disorders.
More Related Videos
06:54Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
07:05TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing
Published on: February 26, 2021
Related Concept Videos
The Tumor Microenvironment
The Tumor Microenvironment
Regulation of Angiogenesis and Blood Supply
TGF - β Signaling Pathway
Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Cadherins in Tissue Organization
Cell Sorting During Development
Cell sorting plays an...