Basic fibroblast growth factor in Dupuytren's contracture.
Lesions excised from nine patients undergoing surgery for Dupuytren's contracture (DC) and three normal fascia were examined for the presence of the angiogenic protein basic fibroblast growth factor (basic FGF). Endothelial cell proliferation assays established basic FGF-like activity in extracts of DC. Western blotting confirmed the presence of an 18,000-dalton protein which was localized in the lesions by immunohistochemical staining. All of the cells implicated in the progression of the disease (endothelial cells, fibroblasts, and myofibroblasts) contain the growth factor. Endothelial cells within the narrowed or occluded vessels, as well as fibroblasts surrounding these vessels, stained intensely positive. In situ hybridization using an antisense probe for human basic FGF and its receptor's (FGFR-1) mRNA established the major difference between normal and DC tissues: their levels are significantly higher than in the normal tissues. Thus the cells in DC also express both basic FGF and FGFR-1, suggesting a potential autocrine/paracrine role for basic FGF in the pathogenesis of DC. This finding is thus the first description of a nontumoral proliferative disease that can be directly associated with increased basic FGF mRNA. The possibility that therapies can be developed on the basis that basic FGF and its receptor are expressed in DC is discussed.
Gonzalez
A M
AM
Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
Buscaglia
M
M
Fox
R
R
Isacchi
A
A
Sarmientos
P
P
Farris
J
J
Ong
M
M
Martineau
D
D
Lappi
D A
DA
Baird
A
A
D004387:Dupuytren Contracture / Q000378:metabolism* / Q000473:pathology; D004727:Endothelium / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009693:Nucleic Acid Hybridization; D011956:Receptors, Cell Surface / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor
D006133:Growth Substances; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2