Glomerular endothelial cell proteoglycans--regulation by TGF-beta 1.
Glomerular endothelial cells (G-Endo) may participate in the synthesis of glomerular basement membrane. We studied the metabolism of proteoglycans and its regulation by TGF-beta 1 in bovine G-Endo. The synthesis of cell layer and medium-associated [35S]SO4-labeled macromolecules was significantly increased by TGF-beta 1. On ion exchange chromatography, 80-90% of the 35S-labeled macromolecules in the control medium and cell layer were found to be proteoglycans; TGF-beta 1 increased their synthesis by 1.8-fold but did not alter the anionic charge density. On dissociative Sepharose CL-4B chromatography, the medium proteoglycans were distributed into two peaks of Kav 0.22 (M-I) and 0.44 (M-II). Digestion procedures showed that 39% and 57% of peaks M-I and M-II consisted of HSPG, the remainder being CS/DSPG. The HSPG in peak M-II has the same hydrodynamic size as HSPG present in bovine glomerular basement membrane (N. Parthasarathy and R. G. Spiro, 1987, J. Biol. Chem. 259:12749). Cell layer proteoglycans also resolved into two peaks of Kav 0.33 (C-I) and 0.63 (C-II), respectively, on Sepharose CL-4B chromatography; 39 and 45% of these peaks were made of HSPG. TGF-beta 1 increased the synthesis of CS/DSPG in the media by three-fold without affecting the synthesis of HSPG. Our data suggest that G-Endo may participate in synthesis of glomerular matrix HSPG under physiologic conditions; regulation of G-Endo proteoglycans by TGF-beta 1 may be of relevance in glomerular diseases characterized by matrix expansion.
Kasinath
B S
BS
Department of Medicine, University of Texas Health Science Center, Audie L. Murphy Memorial Veterans' Administration Hospital, San Antonio.
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004727:Endothelium / Q000737:chemistry; D006497:Heparan Sulfate / Q000378:metabolism; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000166:cytology; D011509:Proteoglycans / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D006497:Heparan Sulfate; D011509:Proteoglycans; D016212:Transforming Growth Factor beta