TY - JOUR
T1 - Fibroblast growth factor-2 stimulates embryonic cardiac mesenchymal cell proliferation
AU - Choy, Michael
AU - Oltjen, Sharon L.
AU - Otani, Yvonne S.
AU - Armstrong, Margaret T.
AU - Armstrong, Peter B.
PY - 1996/6
Y1 - 1996/6
N2 - The proliferation response of stage 36 chick atrioventricular valve mesenchymal cells to fibroblast growth factor-2 (FGF-2) was studied in the tissue-like environment of three-dimensional cell aggregates maintained in organ culture. The mitogenic effects of FGF-2 on mesenchymal tissue depended on the FGF-2-stimulated formation of a fibronectin-containing extracellular matrix. The matrix was absent in unstimulated aggregates, and co-localized with regions of actively proliferating cells in stimulated aggregates. Inhibition of fibronectin matrix formation by the inclusion of Arg-Gly-Asp- containing peptides, which compete with fibronectin for binding to the cell surface α5β1 integrin receptors, abolished the proliferation effects of FGF-2. Inhibition of sulfation of cell surface glycosaminoglycans by treatment with sodium chlorate significantly reduced both the formation of the fibronectin matrix and cell proliferation in response to FGF-2, suggesting an involvement of the low-affinity sulfated glycosaminoglycan FGF receptor system. Thus, the FGF-stimulated growth of embryonic atrioventricular valve mesenchyme in vitro involves the production of a fibronectin matrix. We suggest that the stimulation of the fibronectin matrix represents an essential element in growth factor signaling of mesenchymal tissue, with the matrix serving as an anchorage substratum for the proliferating cells.
AB - The proliferation response of stage 36 chick atrioventricular valve mesenchymal cells to fibroblast growth factor-2 (FGF-2) was studied in the tissue-like environment of three-dimensional cell aggregates maintained in organ culture. The mitogenic effects of FGF-2 on mesenchymal tissue depended on the FGF-2-stimulated formation of a fibronectin-containing extracellular matrix. The matrix was absent in unstimulated aggregates, and co-localized with regions of actively proliferating cells in stimulated aggregates. Inhibition of fibronectin matrix formation by the inclusion of Arg-Gly-Asp- containing peptides, which compete with fibronectin for binding to the cell surface α5β1 integrin receptors, abolished the proliferation effects of FGF-2. Inhibition of sulfation of cell surface glycosaminoglycans by treatment with sodium chlorate significantly reduced both the formation of the fibronectin matrix and cell proliferation in response to FGF-2, suggesting an involvement of the low-affinity sulfated glycosaminoglycan FGF receptor system. Thus, the FGF-stimulated growth of embryonic atrioventricular valve mesenchyme in vitro involves the production of a fibronectin matrix. We suggest that the stimulation of the fibronectin matrix represents an essential element in growth factor signaling of mesenchymal tissue, with the matrix serving as an anchorage substratum for the proliferating cells.
KW - Anchorage dependence
KW - Atrioventricular valves
KW - Cardiac development
KW - Cell proliferation
KW - Chick
KW - Endocardial cushions
KW - Extracellular matrix
KW - Fibronectin
KW - Heparan sulfate proteoglycan
KW - High-affinity receptor
KW - Low-affinity receptor
KW - Mesenchymal cells
UR - http://www.scopus.com/inward/record.url?scp=0029898272&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029898272&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0177(199606)206:2<193::AID-AJA8>3.0.CO;2-D
DO - 10.1002/(SICI)1097-0177(199606)206:2<193::AID-AJA8>3.0.CO;2-D
M3 - Article
C2 - 8725286
AN - SCOPUS:0029898272
VL - 206
SP - 193
EP - 200
JO - Developmental Dynamics
JF - Developmental Dynamics
SN - 1058-8388
IS - 2
ER -