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血清外泌体中的 CD14 和 CD26 与 2 型糖尿病有关,外泌体胱抑素 C 和 CD14 与代谢综合征和血浆致动脉粥样硬化指数有关。

CD14 and CD26 from serum exosomes are associated with type 2 diabetes, exosomal Cystatin C and CD14 are associated with metabolic syndrome and atherogenic index of plasma.

机构信息

Laboratorio de Investigación en Epidemiología Clínica y Molecular, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México.

Laboratorio del Metabolismo de RNA y Vesículas Extracelulares, Instituto Nacional de Medicina Genómica (INMEGEN), México, México.

出版信息

PeerJ. 2022 Jul 12;10:e13656. doi: 10.7717/peerj.13656. eCollection 2022.

Abstract

BACKGROUND

Exosomes are microvesicles that actively participate in signaling mechanisms and depending on their content can contribute to the development of different pathologies, such as diabetes and cardiovascular disease.

OBJECTIVE

The aim of this study was to evaluate the association of cystatin C, CD26, and CD14 proteins in serum exosomes from patients with Type 2 Diabetes (T2D), metabolic syndrome (MetS), and atherogenic index of plasma (AIP).

METHODS

Serum exosomes were isolated by ultracentrifugation from 147 individuals with and without diabetes. Both anthropometric and metabolic parameters were registered from everyone. The levels of exosomal proteins cystatin C, CD26, and CD14 were quantified by ELISA. The association between protein levels and T2D or atherogenic risk factors was analyzed by linear regression and generalized regression models.

RESULTS

We observed a significant correlation of increased glucose with elevated levels of Cystatin C, and an effect of T2D on the levels of CD26 (β = 45.8 pg/µg;  = 0.001) and CD14 (β = 168 pg/µg;  < 0.001) compared to subjects without T2D. CD14 was significantly related to T2D, metabolic syndrome, glucose, and the Atherogenic Index of Plasma (AIP). Additionally, we observed a significant effect of metabolic syndrome MetS on the increase of exosomal Cystatin C and CD14.

CONCLUSIONS

T2D may contribute to the increase of CD14 protein contained in exosomes, as well as to the predisposition of atherogenic events development due to its relationship with the increase in serum triglyceride concentrations and the AIP score. Finally, the increased levels of CD14 and Cystatin C in exosomes are related to MetS. The analysis of exosome contents of diabetic patients remains an incipient field, so extensive characterization is crucial for their use as biomarkers or to analyze their possible contribution to diabetic complications.

摘要

背景

外泌体是一种能够积极参与信号转导机制的微小囊泡,根据其内容的不同,可能会导致糖尿病和心血管疾病等不同疾病的发生和发展。

目的

本研究旨在评估 2 型糖尿病(T2D)、代谢综合征(MetS)和血浆致动脉粥样硬化指数(AIP)患者血清外泌体中胱抑素 C、CD26 和 CD14 蛋白的相关性。

方法

采用超速离心法从 147 例糖尿病患者和非糖尿病患者的血清中分离外泌体。记录每个人的人体测量和代谢参数。采用 ELISA 法测定外泌体蛋白胱抑素 C、CD26 和 CD14 的水平。采用线性回归和广义回归模型分析蛋白水平与 T2D 或致动脉粥样硬化危险因素之间的关系。

结果

我们观察到葡萄糖水平升高与胱抑素 C 水平升高显著相关,与无 T2D 患者相比,T2D 对 CD26(β=45.8 pg/μg;=0.001)和 CD14(β=168 pg/μg;<0.001)水平有显著影响。CD14 与 T2D、代谢综合征、葡萄糖和血浆致动脉粥样硬化指数(AIP)显著相关。此外,我们观察到代谢综合征(MetS)对外泌体胱抑素 C 和 CD14 水平升高有显著影响。

结论

T2D 可能导致外泌体中 CD14 蛋白含量增加,同时由于其与血清甘油三酯浓度和 AIP 评分增加有关,从而增加致动脉粥样硬化事件的发生倾向。最后,外泌体中 CD14 和胱抑素 C 水平的升高与 MetS 有关。对糖尿病患者外泌体内容物的分析仍处于初始阶段,因此广泛的特征分析对于将其用作生物标志物或分析其对糖尿病并发症的可能贡献至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b499/9285478/f783a5c7f782/peerj-10-13656-g001.jpg

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