MicroRNA-155 mediates endogenous angiotensin II type 1 receptor regulation: implications for innovative type 2 diabetes mellitus management

Figure 1 Schematic depiction of coordinated repression of multiple miR-155 targets relevant for T2DM. Translational repression of AGTR1, ARG2, CACNA1C, and ETS-1 reshapes RAAS towards cardio-, vasculo-, and renoprotective phenotypes. BACH1 and SOCS1 repression promotes cytoprotective phenotypes and preserves β-cell function. C/EBPβ, HDAC4, and SOCS1 repression improves glucose homeostasis, enhances insulin signaling, and reverses insulin resistance. Aging, obesity, sarcopenia, AT1R 1169C SNP, and ACEi/ARB treatment negatively impact miR-155 levels and/or function while MR antagonists, metformin, GLP-1 agonists, and verapamil exert beneficial effects. Red arrows or lines represent downregulation, lower Level, inhibition, repression. Green arrows or lines represent increased Level or stimulatory/beneficial action. ACEi: Angiotensin-converting enzyme inhibitors; AGTR1: Angiotensin II type 1 receptor gene; Ang II: Angiotensin II; ARB: Angiotensin II type 1 receptor blockers; ARG2: Arginase 2; AT1/2R: Angiotensin II type 1/2 receptor; BACH1: BTB and CNC homology 1, basic leucine zipper transcription factor 1; CACNA1C (Cav1.2): L-type calcium channel subunit; C/EBPβ: CCAAT/enhancer-binding protein β; eNOS: Endothelial nitric oxide synthetase; EPO: Erythropoietin; ETS-1: E26 Transformation-specific Sequence-1; GLP-1: Glucagon-like peptide 1; GLUT4: Glucose transporter type 4; HO-1: Heme oxygenase 1; HDAC4: Histone Deacetylase 4; IRS-1: Insulin receptor substrate-1; LTCC: L-type Calcium Channel; MasR: Mas Receptor; MicroRNA-155: MiR-155; MR: Mineralocorticoid receptor; NO: Nitric oxide; RAAS: Renin-Angiotensin Aldosterone System; ROS: Reactive oxygen species; SOCS1: Suppressor of cytokine signaling 1; SNP: Single nucleotide polymorphism; T2DM: Type 2 Diabetes Mellitus.