Expression of alpha-actinin-4 in human diabetic nephropathy.
BACKGROUND
Alpha-actinin-4 is an actin filament crosslinking protein that interacts with intercellular adhesion molecules. Recent animal studies suggested that alpha-actinin-4 is an essential component of the glomerular filtration barrier. However, little is known about its expression in human diabetic nephropathy (DN).


METHODS
Renal biopsy tissues were obtained from 17 patients with DN. We determined the mRNA and protein expression levels of alpha-actinin-4 by in situ hybridization and immunohistochemistry. The histopathological severity of DN was classified into two groups: mild and moderate mesangial expansion groups. We also measured urinary protein excretion and creatinine clearance.


RESULTS
Podocytes were positively stained for alpha-actinin-4 mRNA and protein. In the glomeruli, the percentage of cells positive for alpha-actinin-4 mRNA was significantly lower in moderate mesangial expansion group than in mild mesangial expansion group and control. The percentage of immunohistochemically positive area for alpha-actinin-4 protein in moderate mesangial expansion group was significantly lower than in mild mesangial expansion group and control. The percentage of cells positive for alpha-actinin-4 mRNA and area positive for the protein correlated inversely with severity of proteinuria.


CONCLUSIONS
Our results suggest that low expression levels of alpha-actinin-4 mRNA and protein are linked to the progression of glomerulopathy and proteinuria in human DN.
Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara.
Moritsugu
M
Kimura
Masao
M
Toyoda
Mayuko
M
Kato
Keiko
K
Kobayashi
Makiko
M
Abe
Takako
T
Kobayashi
Masaaki
M
Miyauchi
Naoyuki
N
Yamamoto
Tomoya
T
Umezono
Daisuke
D
Suzuki
D000185:Actinin / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D016022:Case-Control Studies; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
C111453:ACTN4 protein, human; D012333:RNA, Messenger; D000185:Actinin