Long noncoding RNA Airn protects podocytes from diabetic nephropathy lesions via binding to Igf2bp2 and facilitating translation of Igf2 and Lamb2.

Abstract

Diabetic nephropathy (DN) is a severe diabetic microvascular complication with high mortality. Long noncoding RNAs (lncRNAs) are characterized as important regulators of various biological processes by emerging researches, whereas the molecular mechanisms by which lncRNAs participate in DN progression need to be further clarified. Herein, we conducted a study on the regulatory role in DN of an lncRNA named antisense of Igf2r non-protein-coding RNA (Airn). Airn expression was downregulated in renal tissues of diabetic mice, and was negatively related with DN development. Besides, Airn downregulation was detected in high-glucose-stimulated podocytes, resulting in poorer cell viability, a higher tendency to cell apoptosis, and a deficiency of laminin level, while Airn overexpression could significantly alleviate these deleterious effects. Mechanistically, using RNA immunoprecipitation and RNA pull-down assays, we found that Airn could bind to the RNA-binding protein Igf2bp2, thus facilitating translation of Igf2 and Lamb2 to maintain normal podocyte viability and glomerular barrier function. Collectively, our results demonstrate the protective role of lncRNA Airn in podocytes against DN, providing a new insight into DN pathogenesis and molecular therapy.