Tian Lei, Shao Xinghua, Xie Yuanyuan, Wang Qin, Che Xiajing, Zhang Minfang, Xu Weijia, Xu Yao, Mou Shan, Ni Zhaohui
Cell Physiol Biochem. 2017;41(2):769-783. doi: 10.1159/000458737. Epub 2017 Feb 13.
BACKGROUND/AIMS: Kidney injury molecule-1 (KIM-1) is highly expressed in renal tubular cells after injury and is usually regarded as an early biomarker of acute kidney injury(AKI). The aim of this study was to determine the role of KIM-1 in the development of renal tubular injury Methods: Clinical samples, three different animal models and in vitro experiments were utilized to determine the possible mechanism underlying the involvement of KIM-1 in kidney injury.
Both plasma and urinary KIM-1 expression levels were significantly higher in AKI and chronic kidney disease (CKD) patients than in healthy volunteers, and urinary KIM-1 expression was significantly higher in CKD patients than in AKI patients. According to the results of our research involving three different mouse models, KIM-1 expression was significantly increased during the early stage of kidney injury and was persistently elevated in renal fibrosis. Our immunofluorescence staining results indicated that KIM-1-positive tubules were surrounded by macrophage infiltrates in regions of kidney injury. Moreover, our transwell, western blotting and real-time PCR data showed that macrophage migration and phenotype transitions were mediated by KIM-1 through the mitogen-activated protein kinase (MAPK) pathway. MAPK pathway inhibition could significantly reverse the effects of KIM-1 with respect to these macrophage phenotype changes and migration.
KIM-1 expression was markedly elevated in both acute and chronic kidney injury and may play a pivotal role in macrophage activation via the MAPK pathway in kidney disease.
背景/目的：肾损伤分子-1（KIM-1）在损伤后的肾小管细胞中高表达，通常被视为急性肾损伤（AKI）的早期生物标志物。本研究旨在确定KIM-1在肾小管损伤发生发展中的作用。方法：利用临床样本、三种不同的动物模型和体外实验来确定KIM-1参与肾损伤的潜在机制。
AKI和慢性肾脏病（CKD）患者的血浆和尿KIM-1表达水平均显著高于健康志愿者，且CKD患者的尿KIM-1表达显著高于AKI患者。根据我们对三种不同小鼠模型的研究结果，KIM-1表达在肾损伤早期显著增加，并在肾纤维化过程中持续升高。我们的免疫荧光染色结果表明，在肾损伤区域，KIM-1阳性肾小管被巨噬细胞浸润所包围。此外，我们的Transwell实验、蛋白质印迹和实时PCR数据显示，巨噬细胞迁移和表型转变由KIM-1通过丝裂原活化蛋白激酶（MAPK）途径介导。抑制MAPK途径可显著逆转KIM-1对这些巨噬细胞表型变化和迁移的影响。
KIM-1表达在急性和慢性肾损伤中均显著升高，可能通过MAPK途径在肾脏疾病中巨噬细胞激活过程中起关键作用。
