Expression of kidney injury molecule-1 (Kim-1) in relation to necrosis and apoptosis during the early stages of Cd-induced proximal tubule injury.
Expression of kidney injury molecule-1 (Kim-1) in relation to necrosis and apoptosis during the early stages of Cd-induced proximal tubule injury.
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DOI：
10.1016/j.taap.2009.01.016
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发表时间：
2009-08-01
影响因子：
3.8
通讯作者：
Bonventre JV
中科院分区：
文献类型：
--
作者：
Prozialeck WC;Edwards JR;Lamar PC;Liu J;Vaidya VS;Bonventre JV
镉（Cd）是一种具有肾毒性的工业和环境污染物，可引起近端小管的广泛功能障碍。Kim-1是一种跨膜糖蛋白，通常在未损伤的肾脏中检测不到，但在镉诱导的近端小管损伤的早期阶段上调并脱落到尿液中。本研究的目的是研究镉诱导的Kim-1表达增加与近端小管坏死和凋亡细胞死亡之间的关系。成年雄性Sprague-Dawley大鼠皮下注射0.6 mg（5.36 μ mol）Cd/kg，每周5天，持续12周。分析尿液样本中Kim-1水平以及细胞死亡的酶标记物乳酸脱氢酶（LDH）和α-谷胱甘肽-S-转移酶（α-GST）。此外，使用Prozialeck实验室最近开发和验证的程序，通过用乙锭同型二聚体原位灌注肾脏特异性标记坏死细胞。还对肾脏的冷冻切片进行处理，用于Kim-1的免疫荧光可视化和通过TUNEL标记鉴定凋亡细胞。结果表明，镉染毒6周后，尿中Kim-1含量开始明显升高，而尿中总蛋白、α-GST和LDH含量直到染毒8-12周才开始升高。免疫荧光标记研究结果显示，6周和12周后，Kim-1在近端小管上皮细胞中表达，但坏死细胞数量没有增加，12周时凋亡细胞数量仅适度增加。这些结果表明，Cd诱导的Kim-1表达的增加发生在坏死发生之前，并且在近端小管中只有适度水平的凋亡。
Cadmium (Cd) is a nephrotoxic industrial and environmental pollutant that causes a generalized dysfunction of the proximal tubule. Kim-1 is a transmembrane glycoprotein that is normally not detectable in non-injured kidney, but is up-regulated and shed into the urine during the early stages of Cd-induced proximal tubule injury. The objective of the present study was to examine the relationship between the Cd-induced increase in Kim-1 expression and the onset of necrotic and apoptotic cell death in the proximal tubule. Adult male Sprague-Dawley rats were treated with 0.6 mg (5.36 μmoles) Cd/kg, subcutaneously, 5 days per week for up to 12 weeks. Urine samples were analyzed for levels of Kim-1 and the enzymatic markers of cell death, lactate dehydrogenase (LDH) and alpha-glutathione-S-transferase (α-GST). In addition, necrotic cells were specifically labeled by perfusing the kidneys in situ with ethidium homodimer using a procedure that has been recently developed and validated in the Prozialeck laboratory. Cryosections of the kidneys were also processed for the immunofluorescent visualization of Kim-1 and the identification of apoptotic cells by TUNEL labeling. Results showed that significant levels of Kim-1 began to appear in the urine after 6 weeks of Cd treatment, whereas the levels of total protein, α-GST and LDH were not increased until 8–12 weeks. Results of immunofluorescence labeling studies showed that after 6 weeks and 12 weeks, Kim-1 was expressed in the epithelial cells of the proximal tubule, but that there was no increase in the number of necrotic cells, and only a modest increase in the number of apoptotic cells at 12 weeks. These results indicate that the Cd-induced increase in Kim-1 expression occurs before the onset of necrosis and at a point where there is only a modest level of apoptosis in the proximal tubule.
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DOI：
10.1152/ajprenal.00067.2005
发表时间：
2006-05-01
影响因子：
4.2
作者：
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