Immunohistochemical study on caveolin-1alpha in regenerating process of tubular cells in gentamicin-induced acute tubular injury in rats.
Caveolin-1, a principal component of caveolae, modulates growth signaling, endocytosis, and intracellular transport. We examined the expression of caveolin-1alpha and its relation to cell cycle and caveolin-interacting growth factor receptors in regenerating proximal tubules (PTs) after gentamicin-induced acute renal failure in rats. Caveolin-1alpha appeared in regenerating PTs as early as day 4 after last gentamicin, peaked at days 6 to 8, and showed cytoplasmic pattern after day 8. Immunoelectron microscopy revealed caveolin-1alpha-positive caveolae on the cell membrane and in cytoplasms in regenerating PTs at days 4 to 8 and caveolin-positivity confined to cytoplasms after day 10. The number of PT cells with proliferation markers peaked at day 6 and decreased afterwards as expression of cyclin-dependent kinase inhibitors increased. Platelet-derived growth factor receptor-beta (PDGFR-beta) and epidermal growth factor receptor (EGFR) were colocalized with caveolin-1alpha in proliferating PTs as early as day 4. Phosphorylated EGFR increased at day 8 and afterwards when caveolins dissociated from EGFR or decreased. In case of PDGFR-beta, phosphorylation seemed to be associated with the increase and association of caveolins to the receptors. Our results suggest that transient expression of caveolin-1alpha in early regenerating PTs might contribute to the regenerating process of PTs through modulating growth factor receptors.
Fujigaki
Yoshihide
Y
First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, 431-3192 Hamamatsu, Japan. yf0516@hama-med.ac.jp
Sakakima
Masanori
M
Sun
Yuan
Y
Goto
Tetsuo
T
Ohashi
Naro
N
Fukasawa
Hirotaka
H
Tsuji
Takayuki
T
Yamamoto
Tatsuo
T
Hishida
Akira
A
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D015153:Blotting, Western; D021941:Caveolae / Q000648:ultrastructure; D051242:Caveolin 1 / Q000378:metabolism*; D051243:Caveolin 2 / Q000378:metabolism; D002453:Cell Cycle; D066246:ErbB Receptors / Q000378:metabolism; D005839:Gentamicins; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000503:physiopathology*; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism; D008297:Male; D016253:Microscopy, Immunoelectron; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D012038:Regeneration; D013997:Time Factors; D014018:Tissue Distribution
C495537:Cav1 protein, rat; D051242:Caveolin 1; D051243:Caveolin 2; D005839:Gentamicins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D020033:Protein Isoforms; C483803:Egfr protein, rat; D066246:ErbB Receptors; D020797:Receptor, Platelet-Derived Growth Factor beta