RRC ID 43128
Author Secker GA, Shortt AJ, Sampson E, Schwarz QP, Schultz GS, Daniels JT.
Title TGFbeta stimulated re-epithelialisation is regulated by CTGF and Ras/MEK/ERK signalling.
Journal Exp Cell Res
Abstract The complex mechanisms by which transforming growth factor beta (TGFbeta) regulate re-epithelialisation following injury of stratified epithelia are not fully understood. TGFbeta signals via binding to distinct receptors activating downstream effectors, including Smads which initiate transcription of target genes. However, studies have shown that TGFbeta can also signal independently of Smads through MAPK pathways, demonstrating the diversity of TGFbeta signalling. Connective tissue growth factor (CTGF) is strongly induced by and acts downstream of TGFbeta causing pathophysiology in tissues by inducing matrix deposition, conversion of fibroblasts into contractile myofibroblasts (e.g. dermis and corneal stroma) and stimulation of epithelial-to-mesenchymal transition (e.g. kidney and lung) all of which are known to cause fibrosis. However, a role for CTGF in epithelial cell function which does not involve direct contribution to fibrosis has not been demonstrated. We show for the first time that synthesis of CTGF in cultures of human corneal epithelial cells is induced by TGFbeta through the Ras/MEK/ERK MAPK signalling pathway and that this is required for re-epithelialisation to occur through cell migration. These data reveal a novel function for CTGF in the regulation of epithelial tissue repair beyond its established role in fibrosis, and further highlight the complexity of TGFbeta regulation of epithelial cell function.
Volume 314(1)
Pages 131-42
Published 2008-1-1
DOI 10.1016/j.yexcr.2007.09.001
PII S0014-4827(07)00411-9
PMID 17915216
MeSH Cell Line Cell Movement / drug effects Cell Movement / physiology Cells, Cultured Connective Tissue Growth Factor Cornea / cytology Cornea / metabolism* Epithelial Cells / cytology Epithelial Cells / drug effects Epithelial Cells / metabolism* Humans Immediate-Early Proteins / drug effects Immediate-Early Proteins / metabolism* Intercellular Signaling Peptides and Proteins / metabolism* MAP Kinase Kinase 1 / drug effects MAP Kinase Kinase 1 / metabolism MAP Kinase Signaling System / drug effects MAP Kinase Signaling System / physiology* Mitogen-Activated Protein Kinase 3 / drug effects Mitogen-Activated Protein Kinase 3 / metabolism Regeneration / drug effects Regeneration / physiology Transforming Growth Factor beta / metabolism* Transforming Growth Factor beta / pharmacology Up-Regulation / drug effects Up-Regulation / physiology Wound Healing / drug effects Wound Healing / physiology* ras Proteins / drug effects ras Proteins / metabolism
IF 3.329
Times Cited 59
Human and Animal Cells