Cytoprotective role of heme oxygenase (HO)-1 in human kidney with various renal diseases
Cytoprotective role of heme oxygenase (HO)-1 in human kidney with various renal diseases
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DOI：
10.1046/j.1523-1755.2001.01000.x
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发表时间：
2001-11-01
影响因子：
19.6
通讯作者：
Koizumi, S
中科院分区：
文献类型：
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作者：
Morimoto, K;Ohta, K;Koizumi, S
背景我们先前曾报道，肾小球的变化在一个人的肾脏标本与血红素氧合酶-1（HO-1）缺乏症是轻微的，但肾小管间质损伤进展。本研究检测了各种肾脏疾病中HO-1在肾脏中的产生模式。此外，通过比较HO-1的产生和羧甲基赖氨酸（CML）和戊糖苷（pentosidine）的表达（两者都是氧化应激的标志物），评估了HO-1在肾脏中的关键细胞保护作用。共从74例患者中获得肾活检或尸检材料。评估血尿和蛋白尿程度以及尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）、β 2-微球蛋白（β 2 m）和肌酐水平。用HO-1、CML和pentosidine的特异性抗血清进行免疫组化研究。HO-1染色在所有肾脏疾病的肾小管上皮细胞内观察到，但在固有肾小球细胞内未检测到。远端小管内HO-1染色往往比近端小管更强烈。在远端肾小管内，HO-1染色强度与血尿程度或蛋白尿的存在之间无显著相关性。在近端肾小管内，HO-1染色倾向于更强，伴有更严重的血尿、蛋白尿和中度肾小管间质损伤。仅在HO-1缺陷患者的肾小管上皮细胞中观察到CML和戊糖苷酶的强染色。HO-1在保护肾小管免受氧化损伤中起重要作用，因为这些细胞不断暴露于各种氧化应激。这表明，肾小管上皮细胞更容易受到氧化应激，由于缺乏这种关键酶在HO-1缺乏。
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), beta (2)-microglobulin (beta (2)m), 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.