Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients.
Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients.
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DOI：
10.3390/ijms22105263
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发表时间：
2021-05-17
影响因子：
5.6
通讯作者：
Sulaiman N
中科院分区：
文献类型：
--
作者：
Elemam NM;Hasswan H;Aljaibeji H;Sulaiman N
2019 年冠状病毒病 (COVID-19) 全球大流行与多器官衰竭和合并症有关，例如 2 型糖尿病 (T2DM)。年龄、性别和肥胖等风险因素与 COVID-19 感染相关。已知严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 使用多种宿主受体进行病毒进入，例如肺和其他器官中的血管紧张素转换酶 2 (ACE2) 和跨膜蛋白酶丝氨酸 2 (TMPRSS2)。然而，ACE2 可能从表面脱落，在循环中形成可溶性 ACE2 (sACE2)。影响 ACE2 表达的表观遗传因素包括一种称为 microRNA (miRNA) 的小非编码 RNA。在这项研究中，我们旨在探索 sACE2 的状态以及几种上游新型 miRNA 的血清水平，作为可能在 T2DM 患者中发挥潜在作用的非侵入性生物标志物。从 50 名 T2DM 患者和 50 名健康对照中收集血清样本，并使用酶联免疫吸附测定 (ELISA) 定量 sACE2 水平。此外，提取RNA，并进行TaqMan miRNA逆转录定量PCR（RT-qPCR）以测量血清miRNA水平。我们的结果显示 sACE2 在 T2DM 患者中降低，并受到年龄、性别和肥胖水平的影响。此外，通过计算机分析显示，血清中可检测到 4 种 miRNA，它们可能是 ACE2 的上游。其中，无论是否存在糖尿病并发症，糖尿病患者血清中的miR-421水平均降低，并且在不同体重指数（BMI）组中存在差异。其他 3 个 miRNA（miR-3909、miR-212-5p 和 miR-4677-3p）除相互相关外，还显示与年龄、性别、BMI 和血清标志物等多种因素相关。总之，我们的研究揭示了 T2DM 患者循环血清 sACE2 水平下降，并鉴定了 4 种与 T2DM 相关的新 miRNA，它们受到不同临床和人口因素的影响。
The global coronavirus disease 2019 (COVID-19) pandemic was associated with multiple organ failure and comorbidities, such as type 2 diabetes mellitus (T2DM). Risk factors, such as age, gender, and obesity, were associated with COVID-19 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to use several host receptors for viral entry, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the lung and other organs. However, ACE2 could be shed from the surface to be soluble ACE2 (sACE2) in the circulation. The epigenetic factors affecting ACE2 expression include a type of small non-coding RNAs called microRNAs (miRNAs). In this study, we aimed at exploring the status of the sACE2 as well as serum levels of several upstream novel miRNAs as non-invasive biomarkers that might have a potential role in T2DM patients. Serum samples were collected from 50 T2DM patients and 50 healthy controls, and sACE2 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Also, RNA was extracted, and TaqMan miRNA reverse transcription quantitative PCR (RT-qPCR) was performed to measure serum miRNA levels. Our results revealed that sACE2 is decreased in the T2DM patients and is affected by age, gender, and obesity level. Additionally, 4 miRNAs, which are revealed by in silico analysis to be potentially upstream of ACE2 were detectable in the serum. Among them, miR-421 level was found to be decreased in the serum of diabetic patients, regardless of the presence or absence of diabetic complications, as well as being differential in various body mass index (BMI) groups. The other 3 miRNAs (miR-3909, miR-212-5p, and miR-4677-3p) showed associations with multiple factors including age, gender, BMI, and serum markers, in addition to being correlated to each other. In conclusion, our study reveals a decline in the circulating serum levels of sACE2 in T2DM patients and identified 4 novel miRNAs that were associated with T2DM, which are influenced by different clinical and demographic factors.
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