Relationship between chaperones and renin-angiotensin system in biopsied renal tissue from lupus nephritis patients
Relationship between chaperones and renin-angiotensin system in biopsied renal tissue from lupus nephritis patients
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发表时间：
2005
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通讯作者：
G. Yong
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作者：
G. Yong
目的分子伴侣的缺失被认为是系统性红斑狼疮（SLE）和肾小球肾炎发病的机制之一。阻断肾素-血管紧张素系统（RAS）已被应用于狼疮性肾炎（LN）的临床治疗。然而，RAS和分子伴侣之间的关系仍然不清楚。因此，本研究旨在探讨肾脏RAS的激活是否与分子伴侣相关。方法收集27例SLE患者肾活检组织，进行形态计量学分析，免疫组化检测肾小球和肾小管血管紧张素转换酶（ACE）、血管紧张素1型受体（AT 1 R）和血管紧张素2型受体（AT 2 R）、HSP 70和泛素的表达。并进行相关性分析，以探讨疾病活动性、病理改变、RAS活性与分子伴侣表达的关系。TUNEL法检测肾脏细胞凋亡。另9例诊断为肾小球轻微病变者作为对照。根据SLE-DAI，13/27例被归类为活动性，而其他14/27例被归类为非活动性。结果与对照组相比，LN患者Ubiquitin、AT 1 R、AT 2 R、ACE的表达及凋亡细胞数均明显增加，而HSP 70的表达明显降低（P0. 05）。HSP 70在肾小管上皮细胞中的表达与慢性组织学指标相关（r=0.432，P=0.028）。在肾小球和肾小管间质区，尽管ACTIVE组AT 1 R的表达显著低于INACTIVE组，但泛素表达与AT 1 R或AT 2 R均呈正相关（P0.05）。结论分子伴侣和RAS异常参与了LN的发病过程，且相互关系密切。
Objective Abnormalities of molecular chaperones have been regarded as one of the mechanisms involved in the pathogenesis of both systemic lupus erythematosus (SLE) and glomerulonephritis. Blockage of renin-angiotensin system (RAS) has been used in the clinical treatment for lupus nephritis (LN). However, the relationship between RAS and molecular chaperones remains unclarified. Therefore, this study was conducted to investigate whether the activation of renal RAS was correlated with molecular chaperones. Methods Renal biopsy tissue were collected from 27 SLE patients for morphometric analyses, expressions of angiotensin converting enzyme (ACE), angiotensin type 1 and 2 receptors (AT1R and AT2R), HSP70 and ubiquitin in both glomeruli and tubules detected by immunohistochemistry. Correlative analyses were performed to examine the relationship between disease activity, pathological changes, RAS activity and expression of molecular chaperones. The apoptotic cells in the kidney were detected by TUNEL method. Another 9 cases diagnosed as minor glomerular lesion served as control. According to SLE-DAI, 13/27 cases were classified as ACTIVE, while the other 14/27 as INACTIVE. Results In LN patients, expressions of ubiquitin, AT1R, AT2R, ACE and the number of apoptotic cells were significantly increased compared with those of the control, while the HSP70 expression in LN patients was significantly lower (P0.05, respectively). The HSP70 expression in the tubulointerstitium was correlated with the chronic histological index (r=0.432, P=0.028). In both glomerular and tubulointerstitial regions, ubiquitin expression was positively correlated with either AT1R or AT2R (P0.05, respectively) despite that the expression of AT1R was significantly lower in ACTIVE group than that in INACTIVE group. Conclusion Chaperone and RAS abnormalities are involved in the pathogenesis of LN with interrelationship of each other.