Involvement of transglutaminase-2 in pathological changes in renal disease.
BACKGROUND
Transglutaminase (Tg)-2 is shown to be related to renal fibrosis. However, its roles in human kidney disease have not been fully studied.


METHODS
Using immunohistochemistry, we examined Tg-2 expression in renal biopsy specimens from 22 patients with IgA nephropathy (IgAN) and correlated the intensity of Tg-2 staining with clinical and histopathological parameters. We compared the distribution and intensity of Tg-2 staining with those of transforming growth factor (TGF)-beta staining.


RESULTS
In normal human kidneys, Tg-2 staining was not significant. In IgAN kidneys, glomerular Tg-2 staining correlated with serum creatinine (S-Cr), creatinine clearance (Ccr), urinary protein excretion, glomerular sclerosis, and mesangial cell proliferation. Tubulointerstitial Tg-2 correlated with S-Cr, Ccr, N-acetyl-beta-glucosaminidase, urinary beta(2)-microglobulin, and tubulointerstitial injuries. Tg-2 staining in the vicinity of vascular poles of glomeruli preceded the development of mesangial lesions, and was more remarkable in cases with renal impairment. The distribution and intensity of Tg-2 staining were not consistent with those of TGF-beta staining. In glomerular crescents, Tg-2 staining was remarkable.


CONCLUSIONS
The present study showed a correlation between Tg-2 expression and renal function and pathological changes. Tg-2 expression in the vicinity of vascular poles was notable because that may be an initial marker of glomerular injury.
Ikee
Ryota
R
Second Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan. ryota.ikee@tokushukai.jp
Kobayashi
Shuzo
S
Hemmi
Noriaki
N
Saigusa
Takamitsu
T
Namikoshi
Tamehachi
T
Yamada
Muneharu
M
Imakiire
Toshihiko
T
Kikuchi
Yuichi
Y
Suzuki
Shigenobu
S
Miura
Soichiro
S
D000328:Adult; D000368:Aged; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D014018:Tissue Distribution; D011503:Transglutaminases / Q000378:metabolism*
D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins