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Divergent regulation of lncRNA expression by ischemia in adult and aging mice
GeroScience ( IF 5.3 ) Pub Date : 2021-10-26 , DOI: 10.1007/s11357-021-00460-9
Tamás Kaucsár 1 , Beáta Róka 1 , Pál Tod 1, 2 , Phuong Thanh Do 1 , Zoltán Hegedűs 3, 4 , Gábor Szénási 1 , Péter Hamar 1, 2
Affiliation  

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.



中文翻译:

成年和衰老小鼠缺血对 lncRNA 表达的不同调节

老年患者对急性肾损伤 (AKI) 的易感性增加。长链非编码 RNA (lncRNA) 是细胞过程的关键调节因子,并且与衰老和 AKI 有关。我们的目的是研究衰老和缺血再灌注损伤 (IRI) 对 lncRNA 肾脏表达的影响。成年和老年(10 个月和 26-30 个月大)C57BL/6 N 小鼠接受单侧 IRI,然后再灌注 7 天。通过 qPCR 在受伤和对侧对照肾脏中测量 90 个 lncRNA 的肾脏表达和损伤、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 lipocalin-2 排泄增加,但血浆尿素相似。在老年小鼠肾小管细胞坏死和凋亡的对照肾脏中,肾损伤分子-1、纤连蛋白-1、p16和p21的mRNA表达升高。IRI 仅增加老年小鼠的血浆尿素浓度,但损伤、再生和纤维化评分及其 mRNA 标志物在两个年龄组中相似。AK082072 和 Y lncRNA 上调,而 H19 和 RepA 转录本在老年小鼠的对照肾脏中下调。IRI 上调 Miat、Igf2as、SNHG5、SNHG6、RNCR3、Malat1、Air、Linc1633 和 Neat1 v1,同时下调 Linc1242。LncRNAs H19、AK082072、RepA 转录本和 Six3os 受衰老和 IRI 的影响。我们的结果表明,衰老和 IRI 都会改变肾脏 lncRNA 的表达,这表明 lncRNA 在衰老和肾损伤中具有广泛而复杂的作用。

更新日期:2021-10-26
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