Caveolae in mesangial cells and caveolin expression in mesangial proliferative glomerulonephritis

O. Tamai et al., Caveolae in mesangial cells and caveolin expression in mesangial proliferative glomerulonephritis, KIDNEY INT, 59(2), 2001, pp. 471-480
Citations number
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
ISSN journal
0085-2538 → ACNP
Year of publication
471 - 480
SICI code
Background. Caveolae are plasma membrane invaginations that have a diameter of 40 to 60 nm. Recent evidences have demonstrated that caveolae contain a variety of signal transduction molecules. Caveolin is a marker protein of caveolae and has been proposed to play a negative regulatory role in signal transduction. The aim of this study was to investigate the behavior of cav eolae and caveolin in experimental glomerulonephritis, the localization of both platelet-derived growth factor (PDGF) and transforming growth factor-b eta (TGF-beta) receptors in the caveolae membrane, and the regulation of ca veolin expression in cultured mesangial cells. Methods. The expression of caveolin-1 was examined by immunoblotting and im munohistology using anti-caveolin antibody in anti-Thy-1 nephritis. The cav eolae membrane fraction of mesangial cells was isolated by sucrose: gradien t method and expression of PDGF receptor and TGF-beta receptor were detecte d by immunoblotting. The effects of mitogens such as phorbol 12-myristate 1 3-acetate (PMA) and PDGF on the expression of caveolin-1 protein and mRNA w ere also examined in cultured mesangial cells. Results. Caveolin-1 was mainly expressed in glomeruli and was significantly up-regulated in anti-Thy-1 nephritis rat kidney. in cultured mesangial cel ls, the membrane invaginations of caveolae were revealed by electron micros copy. PDGF receptors abounded in the caveolae membrane and rapidly changed their subcellular distribution after ligand stimulation. In contrast, TGF-b eta receptors abounded in the non-caveolae membrane and did not change afte r ligand stimulation. Decreases in caveolin-1 protein, which were associate d with increases in mRNA expression after the exposure of PMA or PDGF-BB, s uggested an increased turnover of caveolin-1 in mesangial cells stimulated by mitogens. Conclusion. To our knowledge, this electron microscopical study is the firs t to demonstrate the presence of caveolae in cultured mesangial cells. Cave olae integrate PDGF receptors, and caveolin-1 may play a role in the pathog enesis of the mesangial proliferative glomerular diseases through PDGF sign aling.