Type 2 Diabetes Monocyte MicroRNA and mRNA Expression: Dyslipidemia Associates with Increased Differentiation-Related Genes but Not Inflammatory Activation

Abstract

There is increasing evidence that inflammatory macrophages in adipose tissue are involved in insulin resistance of type 2 diabetes (T2D). Due to a relative paucity of data on circulating monocytes in T2D, it is unclear whether the inflammatory changes of adipose tissue macrophages are reflected in these easily accessible cells.ObjectiveTo study the expression pattern of microRNAs and mRNAs related to inflammation in T2D monocytes.DesignA microRNA finding study on monocytes of T2D patients and controls using array profiling was followed by a quantitative Real Time PCR (qPCR) study on monocytes of an Ecuadorian validation cohort testing the top over/under-expressed microRNAs. In addition, monocytes of the validation cohort were tested for 24 inflammation-related mRNAs and 2 microRNAs previously found deregulated in (auto)-inflammatory monocytes.ResultsIn the finding study, 142 significantly differentially expressed microRNAs were identified, 15 having the strongest power to discriminate T2D patients from controls (sensitivity 66%, specificity 90%). However, differences in expression of these microRNAs between patients and controls were small. On the basis of >1.4 or <0.6-fold change expression 5 microRNAs were selected for further validation. One microRNA (miR-34c-5p) was validated as significantly over-expressed in T2D monocytes. In addition, we found over expression of 3 mRNAs (CD9, DHRS3 and PTPN7) in the validation cohort. These mRNAs are important for cell morphology, adhesion, shape change, and cell differentiation. Classical inflammatory genes (e.g. TNFAIP3) were only over-expressed in monocytes of patients with normal serum lipids. Remarkably, in dyslipidemia, there was a reduction in the expression of inflammatory genes (e.g. ATF3, DUSP2 and PTGS2).ConclusionsThe expression profile of microRNAs/mRNAs in monocytes of T2D patients indicates an altered adhesion, differentiation, and shape change potential. Monocyte inflammatory activation was only found in patients with normal serum lipids. Abnormal lipid values coincided with a reduced monocyte inflammatory state.

T Cell Deficits and Overexpression of Hepatocyte Growth Factor in Anti-inflammatory Circulating Monocytes of Middle-Aged Patients with Bipolar Disorder Characterized by a High Prevalence of the Metabolic Syndrome

“…We previously found a similar gene expression profile, i.e., a reduced pro-inflammatory cluster 1 and raised HGF expression, in the circulating monocytes of 64 T2D patients (23, 36). These T2D patients were on average 62 years old.…”

A Systematic Study of Dysregulated MicroRNA in Type 2 Diabetes Mellitus

“…The main characteristics extracted from various datasets are summarized in Table 1, which includes the number of patients investigated, the measurement platform, type of sample used and the identity of miRNAs in the study [23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81]. Comparing results from multiple tissues provides an overall view of the impact of miRNAs in T2DM pathology.…”

<p>Impact of Low Interferon-γ and IL-10 Levels on TNF-α and IL-6 Production by PHA-Induced PBMCs in Type 2 Diabetes Mellitus</p>

“…22 It is also found that mRNA and miRNA expression from monocytes is altered, resulting in the upregulation of TNF-α and IL-6 gene expression 23 and downregulation of miR-146a and miR-155 expression, the key regulators of inflammatory process. [24][25][26] IL-10 is an anti-inflammatory cytokine secreted by Treg cells, Th2 cells, B cells, macrophages, and DCs. 27 IL-10 Figure 2 Scatter plots of PHA-induced TNF-α/IFN-γ ratio against the baseline IL-10 level for control subjects ( ) and patients with T2DM ( ).…”