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糖尿病尿外泌体中凝血途径相关蛋白的差异表达。

Differential expression of coagulation pathway-related proteins in diabetic urine exosomes.

机构信息

Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.

Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, 100038, China.

出版信息

Cardiovasc Diabetol. 2023 Jun 22;22(1):145. doi: 10.1186/s12933-023-01887-4.

DOI:10.1186/s12933-023-01887-4
PMID:37349729
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10288686/
Abstract

BACKGROUND

Coagulation function monitoring is important for the occurrence and development of diabetes. A total of 16 related proteins are involved in coagulation, but how these proteins change in diabetic urine exosomes is unclear. To explore the expression changes of coagulation-related proteins in urine exosomes and their possible roles in the pathogenesis of diabetes, we performed proteomic analysis and finally applied them to the noninvasive monitoring of diabetes.

METHODS

Subject urine samples were collected. LC-MS/MS was used to collect the information on coagulation-related proteins in urine exosomes. ELISA, mass spectrometry and western blotting were used to further verify the differential protein expression in urine exosomes. Correlations with clinical indicators were explored, and receiver operating characteristic (ROC) curves were drawn to evaluate the value of differential proteins in diabetes monitoring.

RESULTS

Analyzing urine exosome proteomics data, eight coagulation-related proteins were found in this study. Among them, F2 was elevated in urine exosomes of diabetic patients compared with healthy controls. The results of ELISA, mass spectrometry and western blotting further verified the changes in F2. Correlation analysis showed that the expression of urine exosome F2 was correlated with clinical lipid metabolism indexes, and the concentration of F2 was strongly positively correlated with blood TG levels (P < 0.05). ROC curve analysis showed that F2 protein in urine exosomes had a good monitoring value for diabetes.

CONCLUSION

Coagulation-related proteins were expressed in urine exosomes. Among them, F2 was increased in diabetic urine exosomes and may be a potential biomarker for monitoring diabetic changes.

摘要

背景

凝血功能监测对糖尿病的发生发展具有重要意义。凝血过程涉及 16 种相关蛋白,但糖尿病尿外泌体中这些蛋白如何变化尚不清楚。为了探讨凝血相关蛋白在尿外泌体中的表达变化及其在糖尿病发病机制中的可能作用,我们进行了蛋白质组学分析,并最终将其应用于糖尿病的非侵入性监测。

方法

收集受试者尿液样本。采用 LC-MS/MS 收集尿外泌体中凝血相关蛋白的信息。采用 ELISA、质谱和 Western blot 进一步验证尿外泌体中差异蛋白的表达。探讨与临床指标的相关性,绘制受试者工作特征(ROC)曲线,评估差异蛋白在糖尿病监测中的价值。

结果

分析尿外泌体蛋白质组学数据,本研究发现 8 种凝血相关蛋白。其中,糖尿病患者尿外泌体中的 F2 水平高于健康对照组。ELISA、质谱和 Western blot 结果进一步验证了 F2 的变化。相关性分析表明,尿外泌体 F2 的表达与临床脂代谢指标相关,F2 浓度与血 TG 水平呈强烈正相关(P<0.05)。ROC 曲线分析表明,尿外泌体 F2 蛋白对糖尿病具有良好的监测价值。

结论

凝血相关蛋白在尿外泌体中表达。其中,糖尿病患者尿外泌体中的 F2 增加,可能是监测糖尿病变化的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23d/10288686/d2996c34cee7/12933_2023_1887_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23d/10288686/c94cd11ccf03/12933_2023_1887_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23d/10288686/fa35ffbe1b82/12933_2023_1887_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23d/10288686/5c8fb4671606/12933_2023_1887_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23d/10288686/ebe280eaed8f/12933_2023_1887_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23d/10288686/672341d2e9ce/12933_2023_1887_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23d/10288686/d2996c34cee7/12933_2023_1887_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23d/10288686/c94cd11ccf03/12933_2023_1887_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23d/10288686/fa35ffbe1b82/12933_2023_1887_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23d/10288686/5c8fb4671606/12933_2023_1887_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23d/10288686/ebe280eaed8f/12933_2023_1887_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23d/10288686/672341d2e9ce/12933_2023_1887_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23d/10288686/d2996c34cee7/12933_2023_1887_Fig6_HTML.jpg

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