Institute of Translational Medicine, Semmelweis University, Budapest, Hungary.
Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
Geroscience. 2022 Feb;44(1):429-445. doi: 10.1007/s11357-021-00460-9. Epub 2021 Oct 26.
Elderly patients have increased susceptibility to acute kidney injury (AKI). Long noncoding RNAs (lncRNA) are key regulators of cellular processes, and have been implicated in both aging and AKI. Our aim was to study the effects of aging and ischemia-reperfusion injury (IRI) on the renal expression of lncRNAs. Adult and old (10- and 26-30-month-old) C57BL/6 N mice were subjected to unilateral IRI followed by 7 days of reperfusion. Renal expression of 90 lncRNAs and mRNA expression of injury, regeneration, and fibrosis markers was measured by qPCR in the injured and contralateral control kidneys. Tubular injury, regeneration, and fibrosis were assessed by histology. Urinary lipocalin-2 excretion was increased in old mice prior to IRI, but plasma urea was similar. In the control kidneys of old mice tubular cell necrosis and apoptosis, mRNA expression of kidney injury molecule-1, fibronectin-1, p16, and p21 was elevated. IRI increased plasma urea concentration only in old mice, but injury, regeneration, and fibrosis scores and their mRNA markers were similar in both age groups. AK082072 and Y lncRNAs were upregulated, while H19 and RepA transcript were downregulated in the control kidneys of old mice. IRI upregulated Miat, Igf2as, SNHG5, SNHG6, RNCR3, Malat1, Air, Linc1633, and Neat1 v1, while downregulated Linc1242. LncRNAs H19, AK082072, RepA transcript, and Six3os were influenced by both aging and IRI. Our results indicate that both aging and IRI alter renal lncRNA expression suggesting that lncRNAs have a versatile and complex role in aging and kidney injury. An Ingenuity Pathway Analysis highlighted that the most downregulated H19 may be linked to aging/senescence through p53.
老年患者易发生急性肾损伤（AKI）。长链非编码 RNA（lncRNA）是细胞过程的关键调节因子，与衰老和 AKI 均有关。我们的目的是研究衰老和缺血再灌注损伤（IRI）对肾脏 lncRNA 表达的影响。将成年和老年（10-和 26-30 月龄）C57BL/6N 小鼠单侧 IRI 后进行 7 天再灌注。用 qPCR 测量损伤和对侧对照肾脏中 90 个 lncRNA 的肾表达和损伤、再生和纤维化标志物的 mRNA 表达。通过组织学评估肾小管损伤、再生和纤维化。在 IRI 之前，老年小鼠的尿液中脂联素-2 排泄增加，但血浆尿素相似。在老年小鼠的对照肾脏中，肾小管细胞坏死和凋亡、肾损伤分子-1、纤连蛋白-1、p16 和 p21 的 mRNA 表达增加。IRI 仅在老年小鼠中增加血浆尿素浓度，但两组的损伤、再生和纤维化评分及其 mRNA 标志物相似。AK082072 和 Y lncRNA 在老年小鼠的对照肾脏中上调，而 H19 和 RepA 转录物下调。IRI 上调 Miat、Igf2as、SNHG5、SNHG6、RNCR3、Malat1、Air、Linc1633 和 Neat1 v1，而下调 Linc1242。H19、AK082072、RepA 转录物和 Six3os 这 3 个 lncRNA 受衰老和 IRI 的共同影响。我们的结果表明，衰老和 IRI 均改变肾脏 lncRNA 表达，提示 lncRNA 在衰老和肾损伤中具有广泛而复杂的作用。Ingenuity 通路分析强调，下调最明显的 H19 可能通过 p53 与衰老/衰老相关。
