TGFβ and bFGF synthesis and localization in Dupuytren's disease (nodular palmar fibromatosis) relative to cellular activity, myofibroblast phenotype and oncofetal variants of fibronectin

Autor: Berndt, A., Kosmehl, H., Mandel, U., Gabler, U., Luo, Xinmei, Celeda, D., Zardi, L., Katenkamp, D.
Zdroj: The Histochemical Journal; December 1995, Vol. 27 Issue: 12 p1014-1020, 7p
Abstrakt: Nodular palmar fibromatosis is a self-limited proliferation of fibro-/myofibroblasts associated with growth factor synthesis and abundant fibronectin extracellular matrix deposition. bFGF and TGFβ are potent modulators of fibro-/myofibroblast proliferation and differentiation. Moreover,in vitroinvestigations evidenced a TGFβ1-dependent regulation of alternative splicing of fibronectin mRNA. To investigate a possible implication of these growth factors in the tissue formation process of palmar fibromatosis, TGFβ1/2 and bFGF synthesis, as well as TGFβ1/3 and bFGF tissue distribution, is demonstrated by RNAin situhybridization and/or immunohistochemistry in relation to myofibroblast phenotype development (α-smooth muscle actin, desmin immunohistochemistry), expression of different fibronectin isoforms (ED-A+, ED-B+and oncofetal glycosylated fibronectin immunohistochemistry, fibronectin RNAin situhybridization) and cellular activity (cyclin RNAin situhybridization, Ki-67 immunolabelling). The myofibroblast phenotype (α-smooth muscle actin, desmin), the growth factor synthesis (TGFβ1 and 2, bFGF), fibronectin matrix synthesis (RNAin situhybridization with cDNA) and ED-A+, ED-B+and oncofetal glycosylated fibronectin immunostaining are exclusively localized in the active proliferative nodules (Ki-67 immunolabelling and cyclin mRNA demonstration). Whereas the growth factor synthesis is restricted to the proliferative areas of the fibromatosis only, TGFβ1, TGFβ3 and bFGF proteins can also be detected immunohistochemically with a lower intensity in the surrounding aponeurotic tissue. The spatial correlation of myofibroblast phenotype, TGFβ and bFGF synthesis and the occurrence of the oncofetal molecular fibronectin variants (ED-B+and oncofetal glycosylated fibronectin) in the active proliferative fibromatosis nodules suggests a pathogentic role of these growth factors and matrix components in the tumorous tissue formation process. The presence of the bFGF and TGFβ1/3 proteins in fibroblasts neighbouring the proliferative nodules may point to a recruitment of quiescent aponeurotic fibroblasts in the fibromatous tissue formation process.
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