糖尿病肾病患者血清外泌体通过 miR-4449/HIC1 通路促进细胞焦亡和氧化应激。
Serum exosomes from diabetic kidney disease patients promote pyroptosis and oxidative stress through the miR-4449/HIC1 pathway.
机构信息
Department of Nephrology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, 310006, Hangzhou, Zhejiang, China.
出版信息
Nutr Diabetes. 2021 Nov 3;11(1):33. doi: 10.1038/s41387-021-00175-y.
BACKGROUND
Diabetic kidney disease (DKD) is a major contributor to end-stage renal disease. Several microRNAs (miRNAs) have been found to be enriched in exosomes of DKD patients, but it remains unclear if any of these miRNAs play an important role in the pathogenesis of DKD.
METHODS
Exosomes from diabetic kidney disease (DKD) patients were isolated, and the expression of miR-4449 was measured by qRT-PCR. Reactive oxygen species (ROS) was determined by DCDFA assay kit, and pyroptosis was measured by quantifying the level of activated caspase 1. mRNA and protein levels were quantified by qRT-PCR and WB.
RESULTS
In this study, we demonstrated that miR-4449 is enriched in the serum exosomes of DKD patients, and these exosomes regulate the expression of pro-inflammatory cytokines, ROS levels, and pyroptosis through miR-4449.
CONCLUSIONS
Our study uncovered a novel mechanism for the progression of DKD that is mediated through miR-4449 in serum exosomes, which highlights an important role for exosomes in the pathogenesis of DKD.
背景
糖尿病肾病（DKD）是导致终末期肾病的主要原因之一。已经发现几种 microRNAs（miRNAs）在 DKD 患者的外泌体中富集，但尚不清楚这些 miRNAs 中的任何一种是否在 DKD 的发病机制中发挥重要作用。
方法
分离糖尿病肾病（DKD）患者的外泌体，通过 qRT-PCR 测量 miR-4449 的表达。通过 DCDFA 测定试剂盒测定活性氧（ROS），通过定量激活的 caspase 1 测量细胞焦亡。通过 qRT-PCR 和 WB 定量测定 mRNA 和蛋白水平。
结果
在这项研究中，我们证明了 miR-4449 在 DKD 患者的血清外泌体中富集，并且这些外泌体通过 miR-4449 调节促炎细胞因子、ROS 水平和细胞焦亡的表达。
结论
我们的研究揭示了一种新的 DKD 进展机制，该机制通过血清外泌体中的 miR-4449 介导，这突出了外泌体在 DKD 发病机制中的重要作用。
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