FIBRONECTIN SYNTHESIS BY HUMAN TUBULAR EPITHELIAL-CELLS IN CULTURE - EFFECTS OF PDGF AND TGF-BETA ON SYNTHESIS AND SPLICING

Citation
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
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Urology & Nephrology
Journal title
ISSN journal
0085-2538
Volume
54
Issue
2
Year of publication
1998
Pages
407 - 415
Database
ISI
SICI code
0085-2538(1998)54:2<407:FSBHTE>2.0.ZU;2-M
Abstract
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.