Activation of Wnt/β-Catenin Pathway in Monocytes Derived from Chronic Kidney Disease Patients

被引:22
|
作者
Al-Chaqmaqchi, Heevy Abdulkareem Musa [1 ]
Moshfegh, Ali [2 ,3 ]
Dadfar, Elham [4 ]
Paulsson, Josefin [4 ]
Hassan, Moustapha [5 ]
Jacobson, Stefan H. [6 ]
Lundahl, Joachim [4 ]
机构
[1] Karolinska Inst, Dept Lab Med, Div Expt Canc Med, Clin Res Ctr, Stockholm, Sweden
[2] Karolinska Hosp, CCK, Dept Pathol & Oncol, S-10401 Stockholm, Sweden
[3] Karolinska Inst, Stockholm, Sweden
[4] Karolinska Inst, Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden
[5] Karolinska Univ Hosp Huddinge, Clin Res Ctr KFC, Novum, Stockholm, Sweden
[6] Karolinska Inst, Danderyd Univ Hosp, Div Nephrol, Dept Clin Sci, Stockholm, Sweden
来源
PLOS ONE | 2013年 / 8卷 / 07期
关键词
LEUKOCYTE TRANSENDOTHELIAL MIGRATION; WNT SIGNALING PATHWAY; GENE-EXPRESSION; DENDRITIC CELLS; BETA-CATENIN; IMMUNE DYSFUNCTION; ENDOTHELIAL-CELLS; INFLAMMATION; MACROPHAGES; ADHESION;
D O I
10.1371/journal.pone.0068937
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Patients with chronic kidney disease (CKD) have significantly increased morbidity and mortality resulting from infections and cardiovascular diseases. Since monocytes play an essential role in host immunity, this study was directed to explore the gene expression profile in order to identify differences in activated pathways in monocytes relevant to the pathophysiology of atherosclerosis and increased susceptibility to infections. Monocytes from CKD patients (stages 4 and 5, estimated GFR <20 ml/min/1.73 m(2)) and healthy donors were collected from peripheral blood. Microarray gene expression profile was performed and data were interpreted by GeneSpring software and by PANTHER tool. Western blot was done to validate the pathway members. The results demonstrated that 600 and 272 genes were differentially up- and down regulated respectively in the patient group. Pathways involved in the inflammatory response were highly expressed and the Wnt/beta-catenin signaling pathway was the most significant pathway expressed in the patient group. Since this pathway has been attributed to a variety of inflammatory manifestations, the current findings may contribute to dysfunctional monocytes in CKD patients. Strategies to interfere with this pathway may improve host immunity and prevent cardiovascular complications in CKD patients.
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页数:8
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