Study on inflammation-related genes and microRNAs, with special emphasis on the vascular repair factor HGF and miR-574-3p, in monocytes and serum of patients with T2D

Lucy Baldeón Rojas, Karin Weigelt, Harm de Wit, Behiye Ozcan, Adri van Oudenaren, Fernando Sempértegui, Eric Sijbrands, Laura Grosse, Anton-Jan van Zonneveld, Hemmo A. Drexhage, Pieter J. M. Leenen

Recently, we reported signs of inflammation (raised IL-8, reduced miR-146a) and signs of vascular repair (raised HGF) in the serum of Ecuadorian patients with type 2 diabetes (T2D). In contrast, we found that the circulating monocytes lacked up-regulation of classical inflammatory genes (IL-1B, IL-6, and TNF) and there was even significant down-regulation of PTGS2. Notably, genes and a microRNA involved in adhesion, cell differentiation and morphology (CD9, DHRS3, PTPN7 and miR-34c-5p) were up-regulated in the T2D monocytes, suggesting a role of the anti-inflammatory cells in adhesion, vascular repair and invasion. To determine the gene expression of the vascular repair factor HGF in the circulating monocytes of patients with T2D and to investigate the relationship between HGF and the expression of the other previously tested monocyte genes and the contribution to the raised serum level of HGF. In addition, we tested the level of 6 microRNAs, which were previously found abnormal in the circulating monocytes, in the serum of the patients. A gene and microRNA expression study in monocytes and serum of 64 Ecuadorian patients with T2D (37-85 years) and 44 non-diabetic controls (32-87 years). The gene expression of HGF was significantly raised in the monocytes of the patients with T2D and associated with the expression of genes involved in adhesion, cell differentiation and morphology. HGF gene expression did not correlate with the serum level of HGF. The monocyte expression of pro-inflammatory cytokine genes was also not associated with the serum levels of these cytokines. The level of miR-574-3p was significantly decreased in the serum of the patients with T2D, and correlated in expression with the decreased well-established inflammation-regulating miR-146a. The level of the microRNAs in serum did not correlate with their expression level in monocytes. In circulating monocytes of Ecuadorian T2D patients, the microRNA and gene expression of important inflammatory/chemotactic/motility/vascular repair factors differs from the expression in serum. While monocytes show a gene expression profile compatible with an anti-inflammatory state, serum shows a molecular profile compatible with an inflammatory state. Both compartments show molecular signs of vascular repair support, i.e. up-regulated HGF levels.