High SIPA-1 expression in proximal tubules of human kidneys under pathological conditions
High SIPA-1 expression in proximal tubules of human kidneys under pathological conditions
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病理条件下人肾近曲小管中 SIPA-1 高表达
DOI：
10.1007/s11596-015-1390-9
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发表时间：
2015-02-01
影响因子：
--
通讯作者：
Su, Li
中科院分区：
文献类型：
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作者：
Feng, Ai-ping;Zhang, Qian;Su, Li
系统性红斑狼疮（SLE）和肾透明细胞癌（CC-RCC）是严重的疾病，通常是致命的，并总是伴随着肾脏的病理变化。信号诱导增殖相关蛋白1（SIPA-1）是一种Rap 1GT 3激活蛋白（Rap 1GAP），在小鼠肾脏的正常远端和集合小管中表达。在SIPA-1缺陷小鼠中观察到狼疮样自身免疫性疾病和白血病，提示SIPA-1与人类SLE和癌症的病理相关性。SIPA-1的表达模式尚未确定，这些疾病在人类中的发病机制仍然难以捉摸。在这项研究中，我们使用免疫组织化学和量子点（QD）为基础的免疫荧光染色，以调查SIPA-1在SLE和CC-RCC患者的肾脏标本的表达。采用MTT法和Western blotting法检测SIPA-1过表达对肾细胞增殖和凋亡的影响。半定量逆转录聚合酶链反应（RT-PCR）检测缺氧诱导因子-1 α（HIF-1α）mRNA水平的变化。结果显示，SIPA-1在SLE患者肾单位近端小管和集合小管中表达较正常肾单位高，在CC-RCC患者肾单位近端小管和集合小管中表达较正常肾单位高，在CC-RCC患者肾单位近端小管和集合小管中表达较正常肾单位高。SIPA-1过表达对人肾细胞癌细胞系786-O和大鼠肾上皮细胞系NRK-52 E的增殖和凋亡均无影响，但RT-PCR结果显示，SIPA-1过表达可下调786-O细胞中HIF-1α mRNA的表达。提示SIPA-1可能在肾脏病理变化中起重要作用，并可能为SLE和CC-RCC的诊断提供新的生物学标志物。
Systemic lupus erythematosus (SLE) and clear cell renal cell carcinoma (CC-RCC) are serious disorders and usually fatal, and always accompanied with pathological changes in the kidney. Signal-induced proliferation-associated protein 1 (SIPA-1) is a Rap1GTPase activating protein (Rap1GAP) expressed in the normal distal and collecting tubules of the murine kidney. Lupus-like autoimmune disease and leukemia have been observed in SIPA-1 deficient mice, suggesting a pathological relevance of SIPA-1 to SLE and carcinoma in human being. The expression pattern of SIPA-1 is as yet undefined and the pathogenesis of these diseases in humans remains elusive. In this study, we used both immunohistochemistry and quantum dot (QD)-based immunofluorescence staining to investigate the expression of SIPA-1 in renal specimens from SLE and CC-RCC patients. MTT assay and Western blotting were employed to evaluate the effects of SIPA-1 overexpression on the proliferation and apoptosis of renal cell lines. Semi-quantitative reverse transcriptase-PCR (RT-PCR) was applied to examine the changes of hypoxia-inducible factor-1α (HIF-1α) mRNA level. Results showed that SIPA-1 was highly expressed in the proximal and collecting tubules of nephrons in SLE patients compared to normal ones, and similar results were obtained in the specimens of CC-RCC patients. Although SIPA-1 overexpression did not affect cellular proliferation and apoptosis of both human 786-O renal cell carcinoma cells and rat NRK-52E renal epithelial cell lines, RT-PCR results showed that HIF-1α mRNA level was down-regulated by SIPA-1 overexpression in 786-O cells. These findings suggest that SIPA-1 may play critical roles in the pathological changes in kidney, and might provide a new biomarker to aid in the diagnosis of SLE and CC-RCC.