Hyperglycemia Increased The Expression of CALCRL G Protein-Coupled Receptor in Monocytes from Diabetic Patients
نویسندگان
1 Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
2 Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
3 Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians University Munich, Germany
4 Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
5 Cardiovascular Diseases Research Institute, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
doi
10.22074/cellj.2025.2059066.1843چکیده
Objective: Diabetes is a metabolic disorder with two common categories of complications: microvascular andmacrovascular. Cardiovascular diseases (CVDs), which are linked to inflammation in the blood vessels, are themost important complications of diabetes. G protein-coupled receptors (GPCRs) play a crucial role in initiating theseinflammatory responses. The aim of this study is to identify GPCRs that may respond to high blood glucose in monocytecells and have an effect on regulating vascular inflammation.Materials and Methods: In this in-silico and experimental study, first, RNA sequencing (RNAseq) data from monocytesfrom the blood of diabetic patients were analyzed to find the GPCR most responsive to high blood sugar. Next, theexpression correlation of the candidate GPCR with inflammatory genes was calculated, and expression changes inTHP-1 cells under hyperglycemia were evaluated via quantitative polymerase chain reaction (qPCR). Finally, the effectof the candidate GPCR on down-regulation of NF-kB mRNA expression, generation of reactive oxygen species (ROS),and caspase activity was evaluated.Results: The RNAseq analysis showed that expression of Calcitonin receptor-like (CALCRL), one of the GPCRcandidates, increased in the monocytes of patients with diabetes compared to healthy individuals. The qPCR resultalso indicated that expression of the CALCRL gene increased in THP-1 cells treated with 25 mM D-glucose. Correlationanalyses demonstrated that increased expression of CALCRL is associated with inflammatory pathways, cytokineproduction and secretion, and the cell migration process. Finally, our data indicated that CALCRL downregulationdecreased inflammation related to hyperglycemia, including NF-kB mRNA expression, ROS production, and caspase3/7 activity.Conclusion: Hyperglycemia increased the expression of CALCRL GPCR in the monocytes of diabetic patients. TheCALCRL receptor may play a key role in regulating vascular inflammation in hyperglycemic conditions. TargetingCALCRL may control inflammation in blood cells.
