Glomerular proteinuria induces heme oxygenase-1 gene expression within renal epithelial cells.
To clarify the patterns of heme oxygenase-1 (HO-1) production within the human kidney, we examined HO-1 mRNA expression in various renal diseases and compared the patterns with those of HO-1 protein expression and these data with the clinical features. The degrees of hematuria and proteinuria and the levels of urinary N-acetyl-beta-D-glucosaminidase (NAG), beta(2)-microglobulin (beta(2)-mg), and creatinine were determined. In situ hybridization and immunohistochemical studies were performed to evaluate HO-1 expression. HO-1 mRNA was detectable within tubular, glomerular, and Bowman's epithelial cells and infiltrating macrophages. Within the proximal tubuli, there was a correlation between expression of HO-1 protein and mRNA, but the intensity of HO-1 mRNA expression was much less than expected from the levels of protein. In contrast, both HO-1 protein and mRNA were expressed at significant levels within distal tubuli. Furthermore, there was no correlation with both expressions within distal tubuli. HO-1 mRNA expression within tubular, glomerular, and Bowman's epithelial cells tended to be more intense with greater degrees of proteinuria. However, there was little correlation between the intensity of HO-1 mRNA expression and the degree of hematuria, NAG, and beta(2)-mg. HO-1 plays important roles in maintaining renal functions by protecting renal epithelial cells from glomerular proteinuria, which can become a cause of oxidative stress. Furthermore, from the different expression pattern of HO-1 gene between within the proximal tubuli and within the distal tubuli, renal expression of HO-1 is regulated in a segment-specific manner, with HO-1 thereby playing distinct roles in different segments of the nephron to maintain renal functions.
Shimizu
Masaki
M
Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Japan.
Ohta
Kazuhide
K
Yang
Yonghong
Y
Nakai
Akiko
A
Toma
Tomoko
T
Saikawa
Yutaka
Y
Kasahara
Yoshihito
Y
Yachie
Akihiro
A
Yokoyama
Hitoshi
H
Seki
Hidetoshi
H
Koizumi
Shoichi
S
D000118:Acetylglucosaminidase / Q000737:chemistry; D000293:Adolescent; D000818:Animals; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000737:chemistry; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D009399:Nephrons / Q000378:metabolism; D018384:Oxidative Stress; D011507:Proteinuria / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D001613:beta 2-Microglobulin / Q000378:metabolism
D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D003404:Creatinine; D051547:Heme Oxygenase-1; D000118:Acetylglucosaminidase