Department of Anesthesiology, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Hangzhou, China.
Department of General practice, Qingdao Ninth People's Hospital, 2th Chaocheng Road, Qingdao, Shandong, People's Republic of China.
J Bioenerg Biomembr. 2021 Aug;53(4):393-403. doi: 10.1007/s10863-021-09897-1. Epub 2021 Jun 2.
Inflammation and renal cell apoptosis participate in sepsis-induced acute kidney injury. Previous research found the upregulation of long non-coding RNA Linc-KIAA1737-2 in hypoxia- or inflammation-challenged human proximal tubular epithelial cells, but its role in sepsis-induced acute kidney injury is underexplored. In this research, we found that Linc-KIAA1737-2 could be upregulated in HK-2 human proximal tubular epithelial cells by LPS treatment, and knock-down of this lncRNA significantly attenuated LPS-induced apoptosis in HK-2 cells, while its overexpression showed opposite effect. MiR-27a-3p was confirmed to interact with Linc-KIAA1737-2 in HK-2 cells by RNA pull-down and dual-luciferase assay. MiR-27a-3p mimic transfection significantly attenuated LPS-induced HK-2 cell apoptosis by downregulating the protein levels of TLR4 and NF-κB, which was overturned by overexpression of Linc-KIAA1737-2. Our results suggested that Linc-KIAA1737-2 could promote LPS-induced apoptosis in HK-2 cells, and presumably sepsis-induced acute kidney injury, by regulating the miR-27a-3p/TLR4/NF-κB axis.
炎症和肾细胞凋亡参与脓毒症引起的急性肾损伤。先前的研究发现，长链非编码 RNA Linc-KIAA1737-2 在缺氧或炎症挑战的人近端肾小管上皮细胞中上调，但它在脓毒症引起的急性肾损伤中的作用尚未得到充分探索。在这项研究中，我们发现 LPS 处理可上调 HK-2 人近端肾小管上皮细胞中的 Linc-KIAA1737-2，而该 lncRNA 的敲低显著减弱了 LPS 诱导的 HK-2 细胞凋亡，而其过表达则表现出相反的效果。通过 RNA 下拉和双荧光素酶测定证实 miR-27a-3p 与 HK-2 细胞中的 Linc-KIAA1737-2 相互作用。miR-27a-3p 模拟物转染通过下调 TLR4 和 NF-κB 的蛋白水平显著减弱 LPS 诱导的 HK-2 细胞凋亡，而过表达 Linc-KIAA1737-2 则逆转了这一作用。我们的结果表明，Linc-KIAA1737-2 可能通过调节 miR-27a-3p/TLR4/NF-κB 轴促进 LPS 诱导的 HK-2 细胞凋亡，并推测促进脓毒症引起的急性肾损伤。
