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Higher Serum Angiotensinogen Is an Indicator of IgA Vasculitis with Nephritis Revealed by Comparative Proteomes Analysis.

He X, Yin W, Ding Y, Cui SJ, Luan J, Zhao P, Yue X, Yu C, Laing X, Zhao Y - PLoS ONE (2015)

Bottom Line: A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA.More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV.This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression.

View Article: PubMed Central - PubMed

Affiliation: Clinical research center, Wuhan Children's Hospital, No. 100 Hongkong Rd,Wuhan, China.

ABSTRACT
IgA vasculitis (IgAV), previously named as Henoch-Schönlein purpura, is the most common systematic vasculitis with unknown etiology. Lack of appropriate study system and/or animal model limits the understanding of its molecular pathogenesis and hinders the identification of targets for rational therapy, especially for its long-term complication, IgAV nephritis (IgAVN). In this study, we applied comparative analysis of serum proteomes to obtain an insight about disease pathogenesis. This study has utilized high sensitivity nanoscale ultra performance liquid chromatography-mass spectrometry (nanoLC-MS/MS) to investigate the alterations in serum proteomic profiles in patients with IgAV (n=6), IgAVN (n=6) and healthy subjects (n=7). The differentially expressed proteins were subjected to functional pathway analysis by PANTHER and DAVID software. We identified 107 differentially expressed proteins among three different groups, and functional analysis suggested that, in addition to earlier reported pathways, such as acute phase response, immune response, complement and blood coagulation pathways, hemostasis and Wnt signaling pathway were probably involved in pathogenesis of IgAV. A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA. More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV. This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression.

No MeSH data available.


Related in: MedlinePlus

GO molecular function and biological process associated with the differentially expressed proteins identified in IgAV patients.Pie chart represents biological process and molecular obtained in PANTHER analysis.
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pone.0130536.g002: GO molecular function and biological process associated with the differentially expressed proteins identified in IgAV patients.Pie chart represents biological process and molecular obtained in PANTHER analysis.

Mentions: To further understand the molecular and biological functions of these identified proteins, PANTHER classification system was used and these proteins were mainly classified into metabolic process (21.4%), cellular process (14.3%), immune system process (10.3%), localization (10.3%), response to stimulus (8.7%), and biological regulation (7.9%) (Fig 2). The majority of the identified proteins belonged to 6 major GO molecular functions: catalytic activity (35.3%), binding (23.5%), enzyme regulator activity (11.8%), receptor activity (10.3%), transporter activity (8.8%), and structural molecule activity (7.4%) (Fig 2). In addition, protein classification revealed that a number of proteins were involved in acute phase, defense and immunological responses, such as pregnancy zone protein, zinc-alpha-2-glycoprotein, alpha-1B-glycoprotein, complement 9, galectin-3-binding protein, AHSG, transferring, SAA4, and SAA1. Besides characterize the molecular and biological functions of their proteins, we also used DAVID software to analyze the pathways modulated by these differentially expressed proteins: KEGG category revealed complement and coagulation cascades (p = 6.8E-6, 8.6%) and ECM-receptor interaction (0.046, 4.3%), and blood coagulation pathway was identified in PATHER category (1.1E-5, 8.6%), while Reactome category only revealed homeostasis involved (p = 0.00017, 11.4%). Besides blood coagulation pathway, PATHER also identified Wnt signaling pathway, in which Wnt2, Wnt2B, and adenomatous polyposis coli protein 2 (APC2) were involved. Collectively, these observations suggest that, in addition earlier reported complement and blood coagulation pathways, homeostasis, and Wnt signaling pathways may play previously unsuspected roles in IgAV pathogenesis.


Higher Serum Angiotensinogen Is an Indicator of IgA Vasculitis with Nephritis Revealed by Comparative Proteomes Analysis.

He X, Yin W, Ding Y, Cui SJ, Luan J, Zhao P, Yue X, Yu C, Laing X, Zhao Y - PLoS ONE (2015)

GO molecular function and biological process associated with the differentially expressed proteins identified in IgAV patients.Pie chart represents biological process and molecular obtained in PANTHER analysis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476708&req=5

pone.0130536.g002: GO molecular function and biological process associated with the differentially expressed proteins identified in IgAV patients.Pie chart represents biological process and molecular obtained in PANTHER analysis.
Mentions: To further understand the molecular and biological functions of these identified proteins, PANTHER classification system was used and these proteins were mainly classified into metabolic process (21.4%), cellular process (14.3%), immune system process (10.3%), localization (10.3%), response to stimulus (8.7%), and biological regulation (7.9%) (Fig 2). The majority of the identified proteins belonged to 6 major GO molecular functions: catalytic activity (35.3%), binding (23.5%), enzyme regulator activity (11.8%), receptor activity (10.3%), transporter activity (8.8%), and structural molecule activity (7.4%) (Fig 2). In addition, protein classification revealed that a number of proteins were involved in acute phase, defense and immunological responses, such as pregnancy zone protein, zinc-alpha-2-glycoprotein, alpha-1B-glycoprotein, complement 9, galectin-3-binding protein, AHSG, transferring, SAA4, and SAA1. Besides characterize the molecular and biological functions of their proteins, we also used DAVID software to analyze the pathways modulated by these differentially expressed proteins: KEGG category revealed complement and coagulation cascades (p = 6.8E-6, 8.6%) and ECM-receptor interaction (0.046, 4.3%), and blood coagulation pathway was identified in PATHER category (1.1E-5, 8.6%), while Reactome category only revealed homeostasis involved (p = 0.00017, 11.4%). Besides blood coagulation pathway, PATHER also identified Wnt signaling pathway, in which Wnt2, Wnt2B, and adenomatous polyposis coli protein 2 (APC2) were involved. Collectively, these observations suggest that, in addition earlier reported complement and blood coagulation pathways, homeostasis, and Wnt signaling pathways may play previously unsuspected roles in IgAV pathogenesis.

Bottom Line: A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA.More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV.This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression.

View Article: PubMed Central - PubMed

Affiliation: Clinical research center, Wuhan Children's Hospital, No. 100 Hongkong Rd,Wuhan, China.

ABSTRACT
IgA vasculitis (IgAV), previously named as Henoch-Schönlein purpura, is the most common systematic vasculitis with unknown etiology. Lack of appropriate study system and/or animal model limits the understanding of its molecular pathogenesis and hinders the identification of targets for rational therapy, especially for its long-term complication, IgAV nephritis (IgAVN). In this study, we applied comparative analysis of serum proteomes to obtain an insight about disease pathogenesis. This study has utilized high sensitivity nanoscale ultra performance liquid chromatography-mass spectrometry (nanoLC-MS/MS) to investigate the alterations in serum proteomic profiles in patients with IgAV (n=6), IgAVN (n=6) and healthy subjects (n=7). The differentially expressed proteins were subjected to functional pathway analysis by PANTHER and DAVID software. We identified 107 differentially expressed proteins among three different groups, and functional analysis suggested that, in addition to earlier reported pathways, such as acute phase response, immune response, complement and blood coagulation pathways, hemostasis and Wnt signaling pathway were probably involved in pathogenesis of IgAV. A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA. More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV. This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression.

No MeSH data available.


Related in: MedlinePlus