NDLI: EGFR ligands drive multipotential stromal cells to produce multiple growth factors and cytokines via early growth response-1.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kerpedjieva, Svetoslava S. Kim, Duk Soo Barbeau, Dominique J. Tamama, Kenichi
Description	Country affiliation: United States Author Affiliation: Kerpedjieva SS ( Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.)
Abstract	Cell therapy with adult bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) presents a promising approach to promote wound healing and tissue regeneration. The strong paracrine capability of various growth factors and cytokines is a key mechanism of MSC-mediated wound healing and tissue regeneration, and the goal of this study is to understand the underlying mechanism that supports the strong paracrine machineries in MSCs. Microarray database analyses revealed that early growth response-1 (EGR1) is highly expressed in MSCs. Our previous studies showed that epidermal growth factor (EGF) treatment induces growth factor production in MSCs in vitro. Since EGF strongly upregulates EGR1, we hypothesized that EGF receptor (EGFR)-EGR1 signaling plays a pivotal role in MSC paracrine activity. EGF treatment upregulated the gene expression of growth factors and cytokines, including EGFR ligands in a protein kinase C (PKC)- and/or mitogen-activated protein kinase-extracellular-signal-regulated kinase-dependent manner, and it was reversed by shRNA against EGR1. PKC activator phorbol 12-myristate 13-acetate enhanced EGFR tyrosyl phosphorylation and upregulated the gene expression of growth factors and cytokines in a heparin-binding EGF-like growth factor (HBEGF) inhibitor CRM197 sensitive manner, indicating an involvement of autocrined HBEGF in the downstream of PKC signaling. Moreover, stimulation with growth factors and cytokines induced the expression of EGFR ligands, presumably via EGR1 upregulation. These data indicate EGR1 as a convergence point of multiple signaling pathways, which in turn augments the production of multiple growth factors and cytokines by enhancing the autocrine signaling with EGFR ligands.
File Format	HTM / HTML
ISSN	15473287
e-ISSN	15578534
DOI	10.1089/scd.2011.0711
Journal	Stem Cells and Development
Issue Number	13
Volume Number	21
Language	English
Publisher	Mary Ann Liebert, Inc.
Publisher Date	2012-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cell Biology Discipline Hematology Early Growth Response Protein 1 Metabolism Intercellular Signaling Peptides And Proteins Interleukin-6 Mesenchymal Stromal Cells Receptor, Epidermal Growth Factor Amphiregulin Autocrine Communication Cell Line, Tumor Egf Family Of Proteins Genetics Fibroblasts Cytology Drug Effects Gene Knockdown Techniques Glycoproteins Heparin-binding Egf-like Growth Factor Ligands Map Kinase Signaling System Oligonucleotide Array Sequence Analysis Paracrine Communication Protein Kinase C Rna, Small Interfering Tetradecanoylphorbol Acetate Analogs & Derivatives Pharmacology Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Hematology

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