Department of Endocrinology, The Second People's Hospital of Jingzhou City, Jingzhou, City, 434000, Hubei Province, People's Republic of China.
Department of Nephrology, Jiangsu Province Geriatric Hospital, Geriatric Hospital of Nanjing Medical University, No. 65 Jiangsu Road, Nanjing City, 210009, Jiangsu Province, People's Republic of China.
Inflammation. 2020 Dec;43(6):2147-2155. doi: 10.1007/s10753-020-01282-1.
Diabetic nephropathy (DN), characterized by glomerular injury, is a common complication of both type 1 and type 2 diabetes, accompanied by massive proteinuria. Podocytes are reported to play pivotal roles in maintaining the glomerular filtration barrier. In addition, the expression of long non-coding RNAs (lncRNAs) ANRIL was upregulated in type 2 diabetes patients. Hence, the aim of this study was to investigate the underlying mechanisms implicated the role of LncRNA ANRIL in podocyte injury in DN. The concentration of inflammatory cytokines was quantified by the corresponding enzyme-linked immunosorbent assay (ELISA) kits. The mRNA levels of the target gene were determined by reverse transcription and real-time quantitative PCR (RT-qPCR). The expressions of proteins were evaluated by Western blot. The activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) level were measured by corresponding commercial kits. Finally, the apoptosis of podocytes was analyzed by TUNEL assay. In our study, LncRNA ANRIL was highly expressed in high glucose (HG)-induced podocytes. Moreover, LncRNA ANRIL silencing attenuated HG-induced inflammation, oxidative stress, and apoptosis and induced MME overexpression in podocytes. Interestingly, MME knockdown abolished the suppressive effect of LncRNA ANRIL silencing on HG-induced inflammation, oxidative stress, and apoptosis in podocytes. LncRNA ANRIL silencing alleviates HG-induced inflammation, oxidative stress, and apoptosis via upregulation of MME in podocytes. Hence, LncRNA ANRIL may be a novel and effective target to ameliorate podocyte injury in DN.
糖尿病肾病 (DN) 以肾小球损伤为特征，是 1 型和 2 型糖尿病的常见并发症，伴有大量蛋白尿。足细胞被报道在维持肾小球滤过屏障中起关键作用。此外，长链非编码 RNA (lncRNA) ANRIL 在 2 型糖尿病患者中的表达上调。因此，本研究旨在探讨 LncRNA ANRIL 在 DN 中足细胞损伤中作用的潜在机制。通过相应的酶联免疫吸附测定 (ELISA) 试剂盒定量炎症细胞因子的浓度。通过逆转录和实时定量 PCR (RT-qPCR) 测定靶基因的 mRNA 水平。通过 Western blot 评估蛋白质的表达。通过相应的商业试剂盒测量乳酸脱氢酶 (LDH)、超氧化物歧化酶 (SOD) 和丙二醛 (MDA) 水平的活性。最后，通过 TUNEL 分析检测足细胞的凋亡。在我们的研究中，LncRNA ANRIL 在高糖 (HG) 诱导的足细胞中高度表达。此外，LncRNA ANRIL 沉默减弱了 HG 诱导的炎症、氧化应激和凋亡，并诱导足细胞中 MME 的过表达。有趣的是，MME 敲低消除了 LncRNA ANRIL 沉默对 HG 诱导的足细胞炎症、氧化应激和凋亡的抑制作用。LncRNA ANRIL 通过上调足细胞中的 MME 减轻 HG 诱导的炎症、氧化应激和凋亡。因此，LncRNA ANRIL 可能是改善 DN 中足细胞损伤的一种新的有效靶点。
