Plasma proteomics in septic shock and alcohol-related pancreatitis: a hyaluronan-centered approach.

IF 3.3 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS
Jaap van der Heijden, Asanda Mazubane, Marko Sallisalmi, Egor Vorontsov, Jyrki Tenhunen, Annelie Barrueta Tenhunen
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引用次数: 0

Abstract

Background: Sepsis is a critical condition characterized by a dysregulated immune response to infection. As sepsis develops to septic shock, its most severe form, morbidity and mortality increases. Hyaluronan is a key component of the extracellular matrix and the endothelial glycocalyx. In sepsis, plasma hyaluronan concentrations are increased and correlate with disease severity. In this study we aimed to explore and compare the proteomic profiles of hyaluronan-associated proteins in patients with the dysregulated immune response of septic shock and the sterile inflammation of acute alcohol-related pancreatitis.

Methods: The present study involved proteomic analysis of patients with septic shock (n = 13), pancreatitis (n = 8), and healthy controls (n = 8). LC-MS/MS was conducted for peptide analysis. Hyaluronan-associated proteins were identified using the UniProt REST API, followed by functional and pathway enrichment analyses with GOATOOLS and GSEApy. Statistical analyses, including ANOVA and post hoc tests, were performed using Python and SPSS, with significance set at p < 0.05.

Results: From a total sum of 663 detected unique plasma proteins, 15 were identified as hyaluronan-related proteins. Plasma levels of 11/15 proteins separated septic shock from pancreatitis in a statistically significant manner. Between the groups differences were apparent on day 1 (8 proteins in septic shock versus 3 in pancreatitis) and day 4 (6 proteins in septic shock versus 3 in pancreatitis) relative to controls. Functional enrichment analysis revealed associations with extracellular matrix organization, proteolytic enzyme regulation, and hyaluronan metabolism. Notably, members of the inter-alpha-inhibitor family demonstrated distinct patterns, with ITIH3 levels increasing and ITIH1, ITIH2, and ITIH4 levels decreasing in septic shock compared to controls. Additionally, plasma hyaluronidase inhibition correlated positively with ITIH3 levels.

Conclusion: The present study explored the role of hyaluronan-related proteins in septic shock pathophysiology, revealing potential dysregulation associated with sepsis severity. The decrease in ITIH1, ITIH2 and ITIH4, as compared to the increase in ITIH3, suggest a complex alteration in the protein balance of the IαI-family in sepsis. Overall, the altered proteomic profile of hyaluronan-related proteins as reflected by the GO terms indicates a complex dysregulation not only in hyaluronan metabolism and extracellular matrix, but also in the regulation of several proteolytic enzymes. Future studies on this area are warranted.

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感染性休克和酒精相关性胰腺炎的血浆蛋白质组学:以透明质酸为中心的方法。
背景:脓毒症是一种以对感染的免疫反应失调为特征的危重疾病。当败血症发展为感染性休克时,其最严重的形式、发病率和死亡率都会增加。透明质酸是细胞外基质和内皮糖萼的关键成分。在脓毒症中,血浆透明质酸浓度升高并与疾病严重程度相关。在这项研究中,我们旨在探索和比较脓毒性休克免疫反应失调和急性酒精相关性胰腺炎无菌炎症患者透明质酸相关蛋白的蛋白质组学特征。方法:本研究对感染性休克(n = 13)、胰腺炎(n = 8)和健康对照(n = 8)患者进行蛋白质组学分析。采用LC-MS/MS进行多肽分析。使用UniProt REST API鉴定透明质酸相关蛋白,然后使用GOATOOLS和GSEApy进行功能和途径富集分析。统计分析,包括方差分析和事后检验,使用Python和SPSS进行,显著性设置为p。结果:从663个检测到的独特血浆蛋白中,有15个被鉴定为透明质酸相关蛋白。血浆11/15蛋白水平区分感染性休克与胰腺炎具有统计学意义。与对照组相比,组间差异在第1天(感染性休克组有8个蛋白,胰腺炎组有3个蛋白)和第4天(感染性休克组有6个蛋白,胰腺炎组有3个蛋白)比较明显。功能富集分析显示与细胞外基质组织、蛋白水解酶调节和透明质酸代谢有关。值得注意的是,α -抑制剂家族的成员表现出不同的模式,与对照组相比,感染性休克中ITIH3水平升高,ITIH1、ITIH2和ITIH4水平降低。此外,血浆透明质酸酶抑制与ITIH3水平呈正相关。结论:本研究探讨了透明质酸相关蛋白在脓毒症休克病理生理中的作用,揭示了与脓毒症严重程度相关的潜在失调。ITIH1、ITIH2和ITIH4的减少,与ITIH3的增加相比,提示脓毒症中i α i家族蛋白平衡的复杂改变。总的来说,氧化石墨烯术语所反映的透明质酸相关蛋白的蛋白质组学特征的改变表明,不仅在透明质酸代谢和细胞外基质中存在复杂的失调,而且在几种蛋白水解酶的调节中也存在复杂的失调。今后有必要对这一领域进行研究。
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来源期刊
Clinical proteomics
Clinical proteomics BIOCHEMICAL RESEARCH METHODS-
CiteScore
5.80
自引率
2.60%
发文量
37
审稿时长
17 weeks
期刊介绍: Clinical Proteomics encompasses all aspects of translational proteomics. Special emphasis will be placed on the application of proteomic technology to all aspects of clinical research and molecular medicine. The journal is committed to rapid scientific review and timely publication of submitted manuscripts.
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