Proteomic profiling of saliva reveals association of complement system with primary Sjögren's syndrome.

Proteomic profiling of saliva reveals association of complement system with primary Sjögren's syndrome.
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唾液蛋白质组分析揭示补体系统与原发性干燥综合征的关联

DOI:
10.1002/iid3.529
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发表时间:
2021-12
期刊:
Immunity, inflammation and disease
影响因子:
--
通讯作者:
Huo X
Huo X
中科院分区:
其他
文献类型:
--
作者:
Li M;Qi Y;Wang G;Bu S;Chen M;Yu J;Luo T;Meng L;Dai A;Zhou Y;Liu S;Huo X

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比较实验性干燥综合征(ESS)模型小鼠和健康对照小鼠的唾液蛋白质组,以确定潜在的诊断原发性干燥综合征(PSS)的生物标志物。使用与数据无关的采集技术,从3只ESS和3只正常对照小鼠的唾液中提取蛋白质。用R语言分析差异表达蛋白(DEP)。基因本体论和京都百科全书的基因和基因组路径分析被用来对DEPS进行功能注释。构建了蛋白质-蛋白质相互作用(PPI)网络,并利用字符串网站和Cytoscape软件对核心蛋白质进行了鉴定。采用双抗体夹心法测定唾液中丝裂原G家族成员1(SERPING1)、补体C3、补体因子H(CFH)、纤维蛋白原α(FGA)和纤维蛋白原γ(FGG)的含量。与对照组相比,ESS组小鼠唾液中总共发现了1722个DEP,其中50个的表达水平在两组之间存在显著差异。ESS小鼠唾液中SERPING1、C3、CFH、FGA和FGG表达显著下调,角蛋白4(Krt4)和转谷氨酰胺酶3(TGM3)表达上调。PPI网络分析表明,SERPING1、C3、FGG、FGA、TGM3和HPX是核心蛋白。ESS小鼠唾液中C3、CFH、FGA和SERPING1的表达明显下调。而FGG的表达略有下调,但无显著差异。SERPING1、FGG和FGA可能通过抑制免疫补体系统下调补体C3,从而促进PSS的进展。ESS小鼠唾液蛋白质组与健康对照组有显著差异,提示唾液蛋白质组学是一种有前景的PSS无创性诊断工具。SERPING1、C3、CFH、FGA和FGG是PSS的潜在生物标志物。综上所述,SERPING家族成员1(SERPING1)、C3、纤维蛋白原α(FGA)、纤维蛋白原γ(FGG)和补体因子H(CFH)在ESS模型小鼠唾液中显著降低,可能是PSS的潜在诊断生物标志物。这些蛋白在PSS和其他自身免疫性疾病(特别是系统性红斑狼疮)中的作用,在可能应用于临床诊断和治疗之前,必须在实验和队列研究中得到验证。
To compare the saliva proteomes of experimental Sjögren's syndrome (ESS) model mice and healthy controls to identify potential diagnostic biomarkers for primary Sjögren's syndrome (pSS). Proteins were extracted from the saliva of three ESS and three normal control mice using the data‐independent acquisition technique. R language was used to identify the differentially expressed proteins (DEPs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to functionally annotate the DEPs. The protein–protein interaction (PPI) network was constructed and the core proteins were identified with the STRING website and Cytoscape software. The concentrations of Serpin family G member 1 (SERPING1), C3, complement factor H (CFH), fibrinogen alpha (FGA), and fibrinogen gamma (FGG) in saliva were determined by ELISA. A total of 1722 DEPs were identified in the saliva of the ESS mice relative to the controls, of which 50 showed significantly different expression levels between the two groups. SERPING1, C3, CFH, FGA, and FGG were significantly downregulated, and keratin 4 (Krt4) and transglutaminase 3 (TGM3) were upregulated in the saliva of ESS mice. The PPI network showed that SERPING1, C3, FGG, FGA, TGM3, and hemopexin (HPX) were the core proteins. ELISA results showed that the expression of C3, CFH, FGA, and SERPING1 were significantly downregulated in the saliva of ESS mice. However, the expression of FGG was a little downregulated but with no significant difference. SERPING1, FGG, and FGA may downregulate the complement C3 by inhibiting immune complement system, thereby promoting pSS progression. The salivary proteome of ESS mice was markedly different from that of healthy controls, suggesting that salivary proteomics is a promising noninvasive diagnostic tool for pSS. SERPING1, C3, CFH, FGA, and FGG are potential biomarkers of pSS. To summarize our findings, Serpin family G member 1 (SERPING1), C3, fibrinogen alpha (FGA), fibrinogen gamma (FGG), and complement factor H (CFH) were significantly decreased in the saliva of ESS model mice and may therefore be potential diagnostic biomarkers of pSS. The role of these proteins in pSS and other autoimmune diseases (especially systemic lupus erythematosus) will have to be verified in experimental and cohort studies before possible applications in clinical diagnosis and treatment.
DOI: 10.1186/s13075-019-1961-4
发表时间: 2019-07-31
影响因子: 4.9
作者:
Aqrawi, Lara A.;Galtung, Hilde Kanli;Jensen, Janicke Liaaen
通讯作者: Jensen, Janicke Liaaen
DOI: 10.1111/1756-185x.13800
发表时间: 2020-04-01
影响因子: 2.5
作者:
Gorodetskiy, Vadim Romanovich;Probatova, Natalya Alexandrovna;Vasilyev, Vladimir Ivanovich
通讯作者: Vasilyev, Vladimir Ivanovich
利用细胞外囊泡和蛋白质组学分析的提取,在原发性Sjögren综合征中鉴定了潜在的唾液和撕裂生物标志物。
DOI: 10.1186/s13075-017-1228-x
发表时间: 2017-01-25
影响因子: 4.9
作者:
Aqrawi LA;Galtung HK;Vestad B;Øvstebø R;Thiede B;Rusthen S;Young A;Guerreiro EM;Utheim TP;Chen X;Utheim ØA;Palm Ø;Jensen JL
通讯作者: Jensen JL
补体分裂产物IC3B和血清C3的血液浓度与全身性红斑狼疮活性的关联。
DOI: 10.1002/art.40747
发表时间: 2019-03
期刊: Arthritis & rheumatology (Hoboken, N.J.)
影响因子: --
作者:
Kim AHJ;Strand V;Sen DP;Fu Q;Mathis NL;Schmidt MJ;Bruchas RR;Staten NR;Olson PK;Stiening CM;Atkinson JP
通讯作者: Atkinson JP
DOI: 10.1371/journal.pone.0118527
发表时间: 2015
期刊: PloS one
影响因子: 3.7
作者:
Ferrín G;Rodríguez-Perálvarez M;Aguilar-Melero P;Ranchal I;Llamoza C;Linares CI;González-Rubio S;Muntané J;Briceño J;López-Cillero P;Montero-Álvarez JL;de la Mata M
通讯作者: de la Mata M