Functional Role of miR-155 in the Pathogenesis of Diabetes Mellitus and Its Complications.

Stanislovas S Jankauskas,Angela Lombardi,Jessica Gambardella,Gaetano Santulli,Celestino Sardu

doi:10.3390/ncrna7030039

Abstract

Substantial evidence indicates that microRNA-155 (miR-155) plays a crucial role in the pathogenesis of diabetes mellitus (DM) and its complications. A number of clinical studies reported low serum levels of miR-155 in patients with type 2 diabetes (T2D). Preclinical studies revealed that miR-155 partakes in the phenotypic switch of cells within the islets of Langerhans under metabolic stress. Moreover, miR-155 was shown to regulate insulin sensitivity in liver, adipose tissue, and skeletal muscle. Dysregulation of miR-155 expression was also shown to predict the development of nephropathy, neuropathy, and retinopathy in DM. Here, we systematically describe the reports investigating the role of miR-155 in DM and its complications. We also discuss the recent results from in vivo and in vitro models of type 1 diabetes (T1D) and T2D, discussing the differences between clinical and preclinical studies and shedding light on the molecular pathways mediated by miR-155 in different tissues affected by DM.

Highlights

The pandemic of diabetes mellitus (DM) represents one of the most important longterm challenges for healthcare systems around the globe [1]
↑miR-155 in type 2 diabetes (T2D) patients with diabetic diabetic retinopathy and plasma retinopathy compared to both controls and
↑miR-155 in type 1 diabetes (T1D) patients compared to controls

Summary

Introduction

The pandemic of diabetes mellitus (DM) represents one of the most important longterm challenges for healthcare systems around the globe [1]. Hereditary factors have been identified as important modulators of individual susceptibility for T2D development and response to lifestyle interventions [13,14,15]. These facts support the demand for further research on the molecular bases of DM and elucidating new factors involved in DM pathogenesis. The pre-miRNA hairpin, denoted as miR-155-5p and miR-155-3p, can give rise to mature miRNAs possessing biological activity. Both arms of the pre-miRNA hairpin can give rise to mature miRNAs possessing the biological activity [35,36,37] They are denoted with the suffix -5p (from the 5 arm) (e.g., miR-155-5p) and -3p (from the 3 arm) (e.g., miR-155-3p) [38]

Findings from Clinical Studies

Main Findings

Physiological Roles of miR-155

Functional Role of miR-155 in DM Complications

Conclusions and Perspectives