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.

中文翻译：

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长链非编码RNA Airn通过与Igf2bp2结合并促进Igf2和Lamb2的翻译，保护足细胞免受糖尿病肾病的损害。

糖尿病肾病（DN）是一种严重的糖尿病微血管并发症，死亡率高。长的非编码RNA（lncRNAs）被新兴研究表征为各种生物学过程的重要调节剂，而lncRNAs参与DN进程的分子机制有待进一步阐明。在本文中，我们对名为Igf2r非蛋白质编码RNA（Airn）反义的lncRNA在DN中的调控作用进行了研究。Airn表达在糖尿病小鼠肾组织中下调，与DN的发展呈负相关。此外，艾恩在高糖刺激的足细胞中检测到下调，导致较差的细胞生存力，较高的细胞凋亡趋势和层粘连蛋白水平不足，而Airn的过表达可显着减轻这些有害作用。从机制上讲，我们使用RNA免疫沉淀和RNA下拉试验发现Airn可以与RNA结合蛋白Igf2bp2结合，从而促进Igf2和Lamb2的翻译，以维持正常的足细胞活力和肾小球屏障功能。总的来说，我们的结果证明了lncRNA Airn在足细胞中对DN的保护作用，为DN的发病机理和分子治疗提供了新的见识。