HB-EGF/HER-1 signaling in bone marrow mesenchymal stem cells: inducing cell expansion and reversibly preventing multilineage differentiation.
Epidermal growth factor receptor-1 (EGFR-1/HER-1/ErbB-1) regulates proliferation and cell fate during epidermal development. HER-1 is activated by several EGF-family ligands including heparin-binding epidermal growth factor-like growth factor (HB-EGF), a mitogenic and chemotactic molecule that participates in tissue repair, tumor growth, and other tissue-modeling phenomena, such as angiogenesis and fibrogenesis. We found that mesenchymal stem cells (MSCs), the precursors of different mesenchymal tissues with a role in processes in which HB-EGF is often involved, normally express HER-1, but not HB-EGF itself. Under the effect of HB-EGF, MSCs proliferate more rapidly and persistently, without undergoing spontaneous differentiation. This effect occurs in a dose-dependent fashion, and is specific, direct, and HER-1 mediated, as it is inhibited by anti-HER-1 and anti-HB-EGF blocking antibodies. Moreover, HB-EGF reversibly prevents adipogenic, osteogenic, and chondrogenic differentiation induced with specific media. These data show that HB-EGF/HER-1 signaling is relevant to MSC biology, by regulating both proliferation and differentiation.
Krampera
Mauro
M
Department of Clinical and Experimental Medicine, Section of Haematology, University of Verona, Italy. mauro.krampera@univr.it
Pasini
Annalisa
A
Rigo
Antonella
A
Scupoli
Maria Teresa
MT
Tecchio
Cristina
C
Malpeli
Giorgio
G
Scarpa
Aldo
A
Dazzi
Francesco
F
Pizzolo
Giovanni
G
Vinante
Fabrizio
F
D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D015398:Signal Transduction / Q000502:physiology*
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors