Insulin growth factor promotes human corneal fibroblast network formation in vitro

Corneal fibroblast cell (CFC) reticulation is involved in the structural development of corneal stroma and in wound healing. In an earlier paper, it was reported that the expression of VEGFR-1 by CFCs is related to their reticulogenic properties in vitro and decreases with the age of the donors. The...

Full description

Saved in:
Bibliographic Details
Published in:Investigative ophthalmology & visual science 2011-09, Vol.52 (10), p.7647-7653
Main Authors: Berthaut, Alexandre, Mirshahi, Pezhman, Benabbou, Nadia, Ducros, Elodie, Agra, Aureliou, Therwath, Amu, Legeais, Jean Marc, Mirshahi, Massoud
Format: Article
Language:English
Subjects:
Cell Movement - physiology
Cells, Cultured
Corneal Keratocytes - cytology
Corneal Keratocytes - metabolism
Corneal Stroma - cytology
Corneal Stroma - metabolism
Cytokines - genetics
Enzyme Inhibitors - pharmacology
Fluorescent Antibody Technique, Indirect
Humans
Insulin-Like Growth Factor I - physiology
MAP Kinase Kinase 1 - metabolism
MAP Kinase Kinase 2 - metabolism
MAP Kinase Signaling System - drug effects
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Wound Healing - physiology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Corneal fibroblast cell (CFC) reticulation is involved in the structural development of corneal stroma and in wound healing. In an earlier paper, it was reported that the expression of VEGFR-1 by CFCs is related to their reticulogenic properties in vitro and decreases with the age of the donors. The present study was focused on the nonreticulogenic corneal fibroblast population and explored whether these cells can be induced to form cell networks in vitro. The network formation was analyzed using an array of signaling pathway inhibitors: wortmannin for PI3 kinase, U0126 for MEK-1/2 kinase, Rottlerin for PKC, farnesyl transferase inhibitor (FTI-277) for Ras, and picropodophyllin (PPP) for IGFR-1. Among the several growth factors studied, IGF seemed to be crucial to cell network formation. The presence of IGF signaling was demonstrated using gene array analysis and was confirmed by RT-PCR and immunocytochemistry and by cell network formation on reduced synthetic basement membrane arrays. The pleiotropic effect of IGF-1 on the cells was analyzed by protein cytokine array. The genesis of reticulation was found to occur via MEK-1/2 and IGFR pathways, since inhibitors of these signaling pathways reduced or prevented cell network formation. The addition of exogenous IGF-1 generated a cell network structure in corneal fibroblasts obtained from healthy donors, indicating the involvement of IGF-1. IGF signaling and the MEK-1/2 pathway are involved in the cell network formation of corneal fibroblast cells from aged donors.
ISSN:1552-5783
1552-5783
DOI:10.1167/iovs.10-5625