A. Burger et al., FIBRONECTIN SYNTHESIS BY HUMAN TUBULAR EPITHELIAL-CELLS IN CULTURE - EFFECTS OF PDGF AND TGF-BETA ON SYNTHESIS AND SPLICING, Kidney international, 54(2), 1998, pp. 407-415
Background. Enhanced synthesis of extracellular matrix proteins includ
ing fibronectin (FN) is associated with the development of sclerosis.
In this context we studied FN synthesis by tubular epithelial cells in
response to transforming growth factor-beta(TGF-beta) and platelet-de
rived growth factor (PDGF). Methods. FN protein synthesis by human tub
ular epithelial cells in culture (TEC) was measured by biosynthetic la
beling and ELISA. Splicing of FN was assessed by RT-PCR and by Norther
n blotting. Results. Cultivated TEC synthesized and released FN, the m
ajority of which was deposited as an unsoluble protein and a minor por
tion (10 to 15%) was released into the supernatant. TGF-beta and, to a
lesser degree, PDGF, up-regulated FN synthesis. All three FN splice v
ariants (EDA, EDB, and IIICS) were produced. PDGF did not influence th
e splicing. TGF-beta preferentially up-regulated the EDA splice varian
t, but had no effect on the splicing of the other domains. Conclusions
. PDGF and TGF-beta both up-regulate FN synthesis of TEC. TGF-beta, bu
t not PDGF, also changed the quality of the de novo synthesized FN, an
d thus has a different role in the development of sclerosis.