Cytoprotective role of heme oxygenase (HO)-1 in human kidney with various renal diseases.
BACKGROUND
We previously reported that glomerular changes in the renal specimen of a human case with heme oxygenase-1 (HO-1) deficiency were mild, but tubulointerstitial injury advanced progressively. This study examined the patterns of HO-1 production in the kidney in various renal diseases. Furthermore, the critical cytoprotective roles of HO-1 were evaluated in the kidney by comparing HO-1 production and expressions of carboxymethyllysine (CML) and pentosidine, both of which are markers of oxidative stress.


METHODS
Renal biopsy or autopsy materials were obtained from a total of 74 patients. Degrees of hematuria and proteinuria and the levels of urinary N-acetyl-beta-D-glucosaminidase (NAG), beta2-microglobulin (beta2m), and creatinine were evaluated. Immunohistochemical studies for HO-1, CML, and pentosidine expressions were performed with their specific antiserum.


RESULTS
HO-1 staining was observed within tubular epithelial cells in all of the renal diseases, but was not detected within intrinsic glomerular cells. HO-1 staining tended to be more intense within distal tubuli than in proximal tubuli. Within distal tubuli, there was no significant correlation between intensity of HO-1 staining and degree of hematuria or presence of proteinuria. Within proximal tubuli, HO-1 staining tended to be more intense with greater degrees of hematuria, presence of proteinuria, and moderate tubulointerstitial damage. Intense staining of CML and pentosidine was observed within renal tubular epithelial cells only in HO-1-deficient patients.


CONCLUSIONS
HO-1 plays important roles in protecting renal tubuli from oxidative injuries, as these cells are constantly exposed to various oxidative stresses. It is suggested that renal tubular epithelia are more susceptible to oxidative stress due to the lack of this critical enzyme in HO-1 deficiency.
Morimoto
K
K
Department of Pediatrics, School of Medicine, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan.
Ohta
K
K
Yachie
A
A
Yang
Y
Y
Shimizu
M
M
Goto
C
C
Toma
T
T
Kasahara
Y
Y
Yokoyama
H
H
Miyata
T
T
Seki
H
H
Koizumi
S
S
D000293:Adolescent; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000032:analysis; D002648:Child; D019610:Cytoprotection; D006417:Hematuria / Q000201:enzymology; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D051547:Heme Oxygenase-1; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology* / Q000503:physiopathology; D007674:Kidney Diseases / Q000201:enzymology* / Q000503:physiopathology; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis; D008565:Membrane Proteins; D011507:Proteinuria / Q000201:enzymology
D008565:Membrane Proteins; C048496:N(6)-carboxymethyllysine; D001120:Arginine; C062187:pentosidine; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D008239:Lysine