Up-regulation of integrin-linked kinase activity in rat mesangioproliferative glomerulonephritis.
This study investigated whether integrin-linked kinase (ILK) is involved in the pathogenesis of chronic glomerulonephritis (GN) by analyzing the expression and activity of glomerular ILK in a chronic rat model of mesangioproliferative GN. Double immunostaining of kidneys obtained at different time points with glomerular cell-specific markers revealed that ILK was primarily expressed by glomerular epithelial cells, and weakly by mesangial cells (MCs) and endothelial cells in control rats, but dramatically increased in a typical mesangial pattern at days 21 and 28 of GN. Semiquantitative assessment indicated that the level of glomerular ILK expression closely parallels the level of accumulation of glomerular extracellular matrix (ECM) as well as fibronectin (FN). Immunoprecipitation and kinase activity assays using isolated nephritic glomeruli indicated a striking increase of ILK activity on days 21 and 28 of GN. Further, cultured rat MCs overexpressing kinase-deficient ILK diminished FN assembly and collagen matrix remodeling as compared with control transfectants. The results showed that glomerular ILK expression and activity are markedly increased in an experimental model of chronic GN. Increased activity of ILK in MCs may contribute to the development of chronic mesangial alterations leading to glomerular scarring.
Kagami
Shoji
S
Department of Pediatrics, Institute of Health Biosciences, The University of Tokushima, Graduate School, Tokushima 770-8503, Japan. kagami@clin.med.tokushima-u.ac.jp
Shimizu
Maki
M
Kondo
Shuji
S
Kitamura
Akiko
A
Urushihara
Maki
M
Takamatsu
Masanori
M
Yamaji
Satoshi
S
Ishigatsubo
Yoshiaki
Y
Kawachi
Hiroshi
H
Shimizu
Fujio
F
D000818:Animals; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology; D005109:Extracellular Matrix / Q000201:enzymology; D005353:Fibronectins / Q000378:metabolism; D005920:Glomerular Mesangium / Q000201:enzymology*; D005921:Glomerulonephritis / Q000201:enzymology* / Q000473:pathology; D047468:Immunoprecipitation; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D000099200:Scaffold Protein ILK
D003094:Collagen; D005353:Fibronectins; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK