MicroRNA in diabetic nephropathy

MicroRNAs are cellular RNA fragments that prevent the production of a particular protein by binding to and destroying the messenger RNA that would have produced the protein. These post translational modifiers have been found to contribute to the disease diabetic nephropathy (expansion of mesangial matrix that ultimately occludes glomerular capillaries) significantly, but their exact role in this renal disease is not well understood. This article describes the study of one such miRNA, miR-29c, which was identified by a comparative miRNA expression array to be prevalent in diabetic environments. The role of this particular miRNA was then studied by observing its expression in kidney cells in db/db mice (models of obesity, and diabetes), and by observing its effects in kidney microvascular endothelial cells and podocytes treated with high glucose in vitro. This microRNA was found to induce apoptosis of these cells (especially podocytes, which wrap around the capillaries of the glomerulus) and cause a buildup of extracellular matrix protein. To verify these results, the miRNA was inhibited, and the glucose induced cells did not apoptose. It was also found that when miR-29c was inhibited, there was reduced albuminuria (plasma protein in the urine) because the podocytes were not destroyed, and a reduction of kidney mesangial matrix accumulation in the db/db mice. These findings determined the large role that miR-29c plays in diabetic nephropathy, which is a major cause of mortality in patients with diabetes mellitus.

This article was very interesting because it specified the effects of a relatively newfound aspect in gene regulation (miDNA) in the pathology of diabetic nephropathy. This study could lead to developments in inhibiting the miRNA so that this condition is treated effectively, and so that mortality rates of patients with diabetes mellitus decrease. Diabetes mellitus patients could have longer life spans, because glomerular capillaries in the kidney would remain unobstructed.

http://www.jbc.org/content/early/2011/02/10/jbc.M110.194969.full.pdf