Activation of Wnt/β-catenin pathway in monocytes derived from chronic kidney disease patients.
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/β-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.
Department of Laboratory Medicine, Division of Experimental Cancer Medicine-Clinical Research Center, Karolinska Institutet, Stockholm, Sweden. Heevy.Al-Chaqmaqchi@ki.se
Heevy Abdulkareem Musa
HA
Al-Chaqmaqchi
Ali
A
Moshfegh
Elham
E
Dadfar
Josefin
J
Paulsson
Moustapha
M
Hassan
Stefan H
SH
Jacobson
Joachim
J
Lundahl
D000368:Aged; D015153:Blotting, Western; D016022:Case-Control Studies; D019070:Cell Lineage / Q000235:genetics; D003720:Densitometry; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D012313:RNA / Q000302:isolation & purification; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000473:pathology*; D014019:Tissue Donors; D015854:Up-Regulation / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics
D012313:RNA