An Integrated Transcriptomic and Proteomic Analysis Identifies Significant Novel Pathways for Henoch‐Schönlein Purpura Nephritis Progression

Abstract

Background. Although Henoch-Schönlein purpura nephritis (HSPN) is characterized by glomerular deposition of aberrantly glycosylated immunoglobulin A1 (IgA1), the underlying mechanism of HSPN progression has not yet been completely elucidated. In this study, we integrated transcriptomic and proteomic analyses to explore the underlying mechanism of HSPN progression. Methods. RNA sequencing and tandem mass tag- (TMT-) based quantitative proteomics were used to gain serum transcriptomic and proteomic profiles of patients with different types of HSPN (3×type 1, 3×type 2, and 3×type 3). Student’s t-tests were performed to obtain the significance of the differential gene expression. The clusterProfiler package was used to conduct the functional annotation of the DEGs for both Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Results. A total of 2315 mRNAs and 30 proteins were differentially expressed between the different types of HSPN. 58 mRNAs and one protein changed continuously during HSPN development and are potential biomarkers for HSPN progression. The validation cohort (another 9 patients) confirmed the high-throughput results of the transcriptomic and proteomic analyses. A total of 385 significant pathways were related to HSPN progression, and four of them were closely related to clinical biochemical indicators and may play an important role in the progression of HSPN. Those pathways reveal that HSPN progression may be related to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury. Conclusions. Four pathways were found to be closely related to HSPN progression, and it seems that HSPN progression is mainly due to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury.

Identification of key genes and imbalance of immune cell infiltration in immunoglobulin A associated vasculitis nephritis by integrated bioinformatic analysis

“…By integrative analysis of transcriptomics and proteomics, Xie et al. identified a cluster of serums mRNAs and proteins and four pathways including JAK-STAT, mTOR, SWI/SNF and Wnt closely related to IgAVN progression ( 4 ). By bioinformatic study of proteins identified by iTRAQ, Gao et al.…”

“…Recently, rapidly evolving bioinformatic and functional analysis play an important role to define the fundamental mechanisms of disease pathogenesis. By integrative analysis of transcriptomics and proteomics, Xie et al identified a cluster of serums mRNAs and proteins and four pathways including JAK-STAT, mTOR, SWI/SNF and Wnt closely related to IgAVN progression (4). By bioinformatic study of proteins identified by iTRAQ, Gao et al revealed that differential genes were mainly enriched in lipid metabolism and adhesion connection pathways, among which CDC42 and CTNNB1 were potential candidates involved in the pathogenesis of IgAVN (5).…”

IgA vasculitis or Henoch-Schönlein purpura: genetics and beyond

“…Since differential gene expression plays an important role in the onset and progression of the disease, at the level of mRNA and protein, a combined approach is needed to better understand the mechanism of onset of the disease, with integration of different "omics" techniques, including proteomics and transcriptomics [28]. Thanks to the use of proteomics, especially targeted proteomics, promising biomarkers can be identified, which can help stratify patients with respect to the risk of developing kidney disease progression and may contribute to the earlier diagnosis of kidney disease [29,30].…”

“…Thanks to the use of proteomics, especially targeted proteomics, promising biomarkers can be identified, which can help stratify patients with respect to the risk of developing kidney disease progression and may contribute to the earlier diagnosis of kidney disease [29,30]. The combined approach, in terms of the integration of transcriptomics and proteomics, reveals new molecular pathways and mechanisms of kidney disease progression in IgAV, which represent potential clues for the development of new therapeutic approaches [28].…”

Plasma Proteomic Analysis Reveals the Potential Role of Lectin and Alternative Complement Pathways in IgA Vasculitis Pathogenesis

“…"Omics" has been widely used in exploring the underlying mechanisms of disease development. Recent reports have investigated omics in IgA vasculitis [6][7][8][9]. We published a metabolomic study that revealed potential biomarkers associated with the progression of IgAV to IgAV with nephritis [10].…”