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

Abstract

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 m2) 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.

CDKN2B expression in adipose tissue of familial combined hyperlipidemia patients

“…This stringency may have precluded the identifi cation of many genes differentially expressed in the upper abdominal subcutaneous fat of FCHL patients at modest-moderate levels, especially as we implemented a stringent FDR threshold (1%) to minimize the risk of identifying false positives. Nonetheless, it is well established that microarray studies using even smaller patient cohorts than that used in the current study have successfully identifi ed important gene expression changes and the nature of the dysfunctional pathways underlying disease (47)(48)(49)(50)(51)(52). Indeed, our approach was vindicated in that we identifi ed 73 differentially expressed FCHL genes that also exhibited altered expression in the subcutaneous periumbilical fat of rather younger (38 ± 9.3 years of age), leaner (27 ± 2.4 kg/m 2 ), and healthier Mexican FCHL patients who had somewhat higher total cholesterol (6.8 ± 1.2 mmol/l) and triglyceride (4.7 ± 2.6 mmol/l) levels ( 7 ) than our patients ( Table 1 ), presumably because they were not on treatment with statins.…”

Vascular Calcification in Chronic Kidney Disease is Induced by Bone Morphogenetic Protein-2 via a Mechanism Involving the Wnt/�-Catenin Pathway

“…In diabetic mice, Msx promotes the nuclear localization of β-catenin, enhances Wnt signaling and induces osteoblast differentiation and osteogenic calcification [24]. Alterations in the Wnt/β-catenin signaling pathway have been implicated in the development of CKD [35]. A recent study showed that Klotho, a coreceptor of fibroblast growth factor-23 that functions as an inhibitor of Wnt signaling, is deficient in CKD [36].…”

Chronic Kidney Disease Induces Inflammatory CD40 + Monocyte Differentiation via Homocysteine Elevation and DNA Hypomethylation

“…Genome-wide gene expression profiles were established from freshly isolated peripheral blood monocytes from CKD stage 4–5 patients and healthy subjects with a median age of 59 years. 27 (more details in Supplement Methods). …”