Cargando…

TM4SF5-Mediated Roles in the Development of Fibrotic Phenotypes

Transmembrane 4 L six family member 5 (TM4SF5) can form tetraspanin-enriched microdomains (TERMs) on the cell's surface. TERMs contain protein-protein complexes comprised of tetraspanins, growth factor receptors, and integrins. These complexes regulate communication between extracellular and in...

Descripción completa

Detalles Bibliográficos
Autores principales: Ryu, Jihye, Lee, Jung Weon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385246/
https://www.ncbi.nlm.nih.gov/pubmed/28458469
http://dx.doi.org/10.1155/2017/5108525
_version_ 1782520567671291904
author Ryu, Jihye
Lee, Jung Weon
author_facet Ryu, Jihye
Lee, Jung Weon
author_sort Ryu, Jihye
collection PubMed
description Transmembrane 4 L six family member 5 (TM4SF5) can form tetraspanin-enriched microdomains (TERMs) on the cell's surface. TERMs contain protein-protein complexes comprised of tetraspanins, growth factor receptors, and integrins. These complexes regulate communication between extracellular and intracellular spaces to control diverse cellular functions. TM4SF5 influences the epithelial-mesenchymal transition (EMT), aberrant multilayer cellular growth, drug resistance, enhanced migration and invasion, circulation through the bloodstream, tumor-initiation property, metastasis, and muscle development in zebrafish. Here, current data on TM4SF5's roles in the development of fibrotic phenotypes are reviewed. TM4SF5 is induced by transforming growth factor β1 (TGFβ1) signaling via a collaboration with epidermal growth factor receptor (EGFR) activation. TM4SF5, by itself or in concert with other receptors, transduces signals intracellularly. In hepatocytes, TM4SF5 expression regulates cell cycle progression, migration, and expression of extracellular matrix components. In CCl(4)-treated mice, TM4SF5, α-smooth muscle actin (α-SMA), and collagen I expression are observed together along the fibrotic septa regions of the liver. These fibrotic phenotypes are diminished by anti-TM4SF5 reagents, such as a specific small compound [TSAHC, 4′-(p-toluenesulfonylamido)-4-hydroxychalcone] or a chimeric antibody. This review discusses the antifibrotic strategies that target TM4SF5 and its associated protein networks that regulate the intracellular signaling necessary for fibrotic functions of hepatocytes.
format Online
Article
Text
id pubmed-5385246
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-53852462017-04-30 TM4SF5-Mediated Roles in the Development of Fibrotic Phenotypes Ryu, Jihye Lee, Jung Weon Mediators Inflamm Review Article Transmembrane 4 L six family member 5 (TM4SF5) can form tetraspanin-enriched microdomains (TERMs) on the cell's surface. TERMs contain protein-protein complexes comprised of tetraspanins, growth factor receptors, and integrins. These complexes regulate communication between extracellular and intracellular spaces to control diverse cellular functions. TM4SF5 influences the epithelial-mesenchymal transition (EMT), aberrant multilayer cellular growth, drug resistance, enhanced migration and invasion, circulation through the bloodstream, tumor-initiation property, metastasis, and muscle development in zebrafish. Here, current data on TM4SF5's roles in the development of fibrotic phenotypes are reviewed. TM4SF5 is induced by transforming growth factor β1 (TGFβ1) signaling via a collaboration with epidermal growth factor receptor (EGFR) activation. TM4SF5, by itself or in concert with other receptors, transduces signals intracellularly. In hepatocytes, TM4SF5 expression regulates cell cycle progression, migration, and expression of extracellular matrix components. In CCl(4)-treated mice, TM4SF5, α-smooth muscle actin (α-SMA), and collagen I expression are observed together along the fibrotic septa regions of the liver. These fibrotic phenotypes are diminished by anti-TM4SF5 reagents, such as a specific small compound [TSAHC, 4′-(p-toluenesulfonylamido)-4-hydroxychalcone] or a chimeric antibody. This review discusses the antifibrotic strategies that target TM4SF5 and its associated protein networks that regulate the intracellular signaling necessary for fibrotic functions of hepatocytes. Hindawi 2017 2017-03-26 /pmc/articles/PMC5385246/ /pubmed/28458469 http://dx.doi.org/10.1155/2017/5108525 Text en Copyright © 2017 Jihye Ryu and Jung Weon Lee. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Ryu, Jihye
Lee, Jung Weon
TM4SF5-Mediated Roles in the Development of Fibrotic Phenotypes
title TM4SF5-Mediated Roles in the Development of Fibrotic Phenotypes
title_full TM4SF5-Mediated Roles in the Development of Fibrotic Phenotypes
title_fullStr TM4SF5-Mediated Roles in the Development of Fibrotic Phenotypes
title_full_unstemmed TM4SF5-Mediated Roles in the Development of Fibrotic Phenotypes
title_short TM4SF5-Mediated Roles in the Development of Fibrotic Phenotypes
title_sort tm4sf5-mediated roles in the development of fibrotic phenotypes
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385246/
https://www.ncbi.nlm.nih.gov/pubmed/28458469
http://dx.doi.org/10.1155/2017/5108525
work_keys_str_mv AT ryujihye tm4sf5mediatedrolesinthedevelopmentoffibroticphenotypes
AT leejungweon tm4sf5mediatedrolesinthedevelopmentoffibroticphenotypes