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尿中α-胰蛋白酶抑制剂家族相关蛋白可作为狼疮疾病活动的生物标志物。

Urine inter-alpha-trypsin inhibitor family-related proteins may serve as biomarkers for disease activity of lupus.

机构信息

Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing, China.

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

出版信息

J Clin Lab Anal. 2022 Sep;36(9):e24622. doi: 10.1002/jcla.24622. Epub 2022 Jul 23.

Abstract

BACKGROUND

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease involving multiple tissues. Inter-Alpha-Trypsin Inhibitor (ITI) family proteins have a role in maintaining tissue homeostasis, but their possible clinical significance in the SLE patients has not been reported. The aim of this study was to analyze and verify the expression of ITI-related proteins in the urine of SLE patients, further explore the features of these proteins in disease activity.

METHODS

Based on label-free proteomics technology and bioinformatics technology, we analyzed the expression of ITI family-related proteins in the urine of lupus. Subsequently, Western-blot and targeted proteomics were used to qualitatively and quantitatively verify the expression of these proteins, respectively.

RESULTS

A total of seven ITI family-related proteins were screened and identified; and six of these proteins were differentially expressed in the urine of SLE patients. Further quantitative analysis showed that the expressions of ITIH2, ECM1, and ITIH5 in urine between active SLE group and stable SLE group were consistent with the preliminary screening results. The expression of ITIH2 and ECM1 in the renal damage group were also consistent with the screening results. Moreover, ITIH2 and ECM1 have a good correlation with disease activity and have a certain correlation with renal damage.

CONCLUSIONS

In this exploratory study, we evaluated the expression of ITI family-related proteins in the urine of SLE and found that urine ITIH2 and ECM1 were closely related to SLE activity, especially kidney damage, providing an experimental basis for further exploration of the potential roles in monitoring lupus and lupus nephritis activity.

摘要

背景

系统性红斑狼疮(SLE)是一种涉及多个组织的慢性炎症性疾病。α-胰蛋白酶抑制剂(ITI)家族蛋白在维持组织内稳态方面发挥作用,但它们在 SLE 患者中的可能临床意义尚未报道。本研究旨在分析和验证 SLE 患者尿液中 ITI 相关蛋白的表达,进一步探讨这些蛋白在疾病活动中的特征。

方法

基于无标记蛋白质组学技术和生物信息学技术,我们分析了狼疮尿液中 ITI 家族相关蛋白的表达。随后,采用 Western-blot 和靶向蛋白质组学技术分别对这些蛋白进行定性和定量验证。

结果

共筛选和鉴定了 7 种 ITI 家族相关蛋白,其中 6 种蛋白在 SLE 患者尿液中表达差异。进一步的定量分析表明,活动期 SLE 组和稳定期 SLE 组尿液中 ITIH2、ECM1 和 ITIH5 的表达与初步筛选结果一致。肾损伤组中 ITIH2 和 ECM1 的表达也与筛选结果一致。此外,ITIH2 和 ECM1 与疾病活动度具有良好的相关性,与肾损伤具有一定的相关性。

结论

在这项探索性研究中,我们评估了 SLE 患者尿液中 ITI 家族相关蛋白的表达,发现尿液 ITIH2 和 ECM1 与 SLE 活性密切相关,尤其是与肾脏损伤相关,为进一步探索其在监测狼疮和狼疮肾炎活动中的潜在作用提供了实验依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c078/9459346/cc528105892a/JCLA-36-e24622-g001.jpg

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