Caveolae in mesangial cells and caveolin expression in mesangial proliferative glomerulonephritis.
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 caveolae and caveolin in experimental glomerulonephritis, the localization of both platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) receptors in the caveolae membrane, and the regulation of caveolin expression in cultured mesangial cells.


METHODS
The expression of caveolin-1 was examined by immunoblotting and immunohistology using anti-caveolin antibody in anti-Thy-1 nephritis. The caveolae membrane fraction of mesangial cells was isolated by sucrose gradient method and expression of PDGF receptor and TGF-beta receptor were detected by immunoblotting. The effects of mitogens such as phorbol 12-myristate 13-acetate (PMA) and PDGF on the expression of caveolin-1 protein and mRNA were 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 cells, the membrane invaginations of caveolae were revealed by electron microscopy. PDGF receptors abounded in the caveolae membrane and rapidly changed their subcellular distribution after ligand stimulation. In contrast, TGF-beta receptors abounded in the non-caveolae membrane and did not change after ligand stimulation. Decreases in caveolin-1 protein, which were associated with increases in mRNA expression after the exposure of PMA or PDGF-BB, suggested an increased turnover of caveolin-1 in mesangial cells stimulated by mitogens.


CONCLUSIONS
To our knowledge, this electron microscopical study is the first to demonstrate the presence of caveolae in cultured mesangial cells. Caveolae integrate PDGF receptors, and caveolin-1 may play a role in the pathogenesis of the mesangial proliferative glomerular diseases through PDGF signaling.
Tamai
O
O
Kasuya Minami Hospital, Fukuoka, Japan. osm@hf.rim.or.jp
Oka
N
N
Kikuchi
T
T
Koda
Y
Y
Soejima
M
M
Wada
Y
Y
Fujisawa
M
M
Tamaki
K
K
Kawachi
H
H
Shimizu
F
F
Kimura
H
H
Imaizumi
T
T
Okuda
S
S
D000818:Animals; D021941:Caveolae / Q000378:metabolism / Q000648:ultrastructure*; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism* / Q000473:pathology*; D007425:Intracellular Membranes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008024:Ligands; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism
C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; D008024:Ligands; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D013755:Tetradecanoylphorbol Acetate