Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Sci Rep. 2017 Oct 9;7(1):12821. doi: 10.1038/s41598-017-13029-4.
Proteins involved in iron homeostasis have been identified as biomarkers for lupus nephritis, a serious complication of systemic lupus erythematosus (SLE). We tested the hypothesis that renal iron accumulation occurs and contributes to renal injury in SLE. Renal non-heme iron levels were increased in the (New Zealand Black x New Zealand White) F1 (NZB/W) mouse model of lupus nephritis compared with healthy New Zealand White (NZW) mice in an age- and strain-dependent manner. Biodistribution studies revealed increased transferrin-bound iron accumulation in the kidneys of albuminuric NZB/W mice, but no difference in the accumulation of non-transferrin bound iron or ferritin. Transferrin excretion was significantly increased in albuminuric NZB/W mice, indicating enhanced tubular exposure and potential for enhanced tubular uptake following filtration. Expression of transferrin receptor and 24p3R were reduced in tubules from NZB/W compared to NZW mice, while ferroportin expression was unchanged and ferritin expression increased, consistent with increased iron accumulation and compensatory downregulation of uptake pathways. Treatment of NZB/W mice with the iron chelator deferiprone significantly delayed the onset of albuminuria and reduced blood urea nitrogen concentrations. Together, these findings suggest that pathological changes in renal iron homeostasis occurs in lupus nephritis, contributing to the development of kidney injury.
铁稳态相关蛋白已被鉴定为狼疮肾炎（系统性红斑狼疮的一种严重并发症）的生物标志物。我们检验了这样一个假说，即铁在肾脏中的蓄积会导致狼疮肾炎的肾脏损伤。与健康的新西兰白（NZW）小鼠相比，狼疮肾炎的（新西兰黑×新西兰白）F1（NZB/W）小鼠模型中肾脏的非血红素铁水平随着年龄和品系的不同而增加。生物分布研究显示，白蛋白尿的 NZB/W 小鼠肾脏中铁蛋白结合铁的蓄积增加，但非转铁蛋白结合铁或铁蛋白的蓄积没有差异。白蛋白尿的 NZB/W 小鼠中铁蛋白的排泄明显增加，表明在滤过之后肾小管的暴露和潜在的摄取增强。与 NZW 小鼠相比，NZB/W 小鼠的肾小管中转铁蛋白受体和 24p3R 的表达减少，而铁蛋白的表达增加，这与铁蓄积增加和摄取途径的代偿性下调一致。用铁螯合剂地拉罗司治疗 NZB/W 小鼠可显著延迟白蛋白尿的发生并降低血尿素氮浓度。综上所述，这些发现表明狼疮肾炎中肾脏铁稳态的病理性改变发生，导致肾脏损伤的发展。
