Cell-Cycle Dysregulation in the Pathogenesis of Diabetic Kidney Disease: An Update

Abstract

In the last few decades, the prevalence of diabetes mellitus (DM) has increased rapidly. Diabetic kidney disease (DKD) is the major cause of end-stage renal disease (ESRD) globally, attributed to hemodynamic changes and chronic hyperglycemia. Recent findings have emphasized the role of cell-cycle dysregulation in renal fibrosis and ESRD. Under normal physiological conditions, most mature renal cells are arrested in the G0 phase of the cell cycle, with a rather low rate of renewal. However, renal cells can bypass restriction points and re-enter the cell cycle under stimulation of injuries induced via metabolic disorders. Mild injuries activate proliferation of renal cells to compensate for cell loss and reinstate renal function, while severe or repeated injuries will lead to DNA damage and maladaptive repair which ultimately results in cell-cycle arrest or overproliferation, and eventually promote renal fibrosis and ESRD. In this review, we focus on the role of cell-cycle dysregulation in DKD and discuss new, emerging pathways that are implicated in the process.