Image1_Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics.tif

Introduction<p>Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), presents significant challenges in patient management and treatment outcomes. The identification of novel LN-related biomarkers and therapeutic targets is critical to enhancing treatment outcomes...

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Main Author: Lisha Mou (151003) (author)
Other Authors: Fan Zhang (46132) (author), Xingjiao Liu (18608059) (author), Ying Lu (66401) (author), Mengli Yue (18608062) (author), Yupeng Lai (12610630) (author), Zuhui Pu (10931751) (author), Xiaoyan Huang (112885) (author), Meiying Wang (1309134) (author)
Published: 2024
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author Lisha Mou (151003)
author2 Fan Zhang (46132)
Xingjiao Liu (18608059)
Ying Lu (66401)
Mengli Yue (18608062)
Yupeng Lai (12610630)
Zuhui Pu (10931751)
Xiaoyan Huang (112885)
Meiying Wang (1309134)
author2_role author
author
author
author
author
author
author
author
author_facet Lisha Mou (151003)
Fan Zhang (46132)
Xingjiao Liu (18608059)
Ying Lu (66401)
Mengli Yue (18608062)
Yupeng Lai (12610630)
Zuhui Pu (10931751)
Xiaoyan Huang (112885)
Meiying Wang (1309134)
author_role author
dc.creator.none.fl_str_mv Lisha Mou (151003)
Fan Zhang (46132)
Xingjiao Liu (18608059)
Ying Lu (66401)
Mengli Yue (18608062)
Yupeng Lai (12610630)
Zuhui Pu (10931751)
Xiaoyan Huang (112885)
Meiying Wang (1309134)
dc.date.none.fl_str_mv 2024-10-21T08:15:35Z
dc.identifier.none.fl_str_mv 10.3389/fimmu.2024.1309447.s004
dc.relation.none.fl_str_mv https://figshare.com/articles/figure/Image1_Integrative_analysis_of_COL6A3_in_lupus_nephritis_insights_from_single-cell_transcriptomics_and_proteomics_tif/27266652
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Immunology
Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
Autoimmunity
Cellular Immunology
Humoural Immunology and Immunochemistry
Immunogenetics (incl. Genetic Immunology)
Innate Immunity
Transplantation Immunology
Tumour Immunology
Immunology not elsewhere classified
Genetic Immunology
Animal Immunology
Veterinary Immunology
systemic lupus erythematosus
kidney disease
lupus nephritis
single-cell RNA sequencing
proteomics
COL6A3
biomarkers
diagnosis
dc.title.none.fl_str_mv Image1_Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics.tif
dc.type.none.fl_str_mv Image
Figure
info:eu-repo/semantics/publishedVersion
image
description Introduction<p>Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), presents significant challenges in patient management and treatment outcomes. The identification of novel LN-related biomarkers and therapeutic targets is critical to enhancing treatment outcomes and prognosis for patients.</p>Methods<p>In this study, we analyzed single-cell expression data from LN (n=21) and healthy controls (n=3). A total of 143 differentially expressed genes were identified between the LN and control groups. Then, proteomics analysis of LN patients (n=9) and control (SLE patients without LN, n=11) revealed 55 differentially expressed genes among patients with LN and control group. We further utilizes protein-protein interaction network and functional enrichment analyses to elucidate the pivotal role of COL6A3 in key signaling pathways. Its diagnostic value is evaluate through its correlation with disease progression and renal function metrics, as well as Receiver Operating Characteristic Curve (ROC) analysis. Additionally, immunohistochemistry and qPCR experiments were performed to validate the expression of COL6A3 in LN.</p>Results<p>By comparison of single-cell and proteomics data, we discovered that COL6A3 is significantly upregulated, highlighting it as a critical biomarker of LN. Our findings emphasize the substantial involvement of COL6A3 in the pathogenesis of LN, particularly noting its expression in mesangial cells. Through comprehensive protein-protein interaction network and functional enrichment analyses, we uncovered the pivotal role of COL6A3 in key signaling pathways including integrin-mediated signaling pathways, collagen-activated signaling pathways, and ECM-receptor interaction, suggesting potential therapeutic targets. The diagnostic utility is confirmed by its correlation with disease progression and renal function metrics of the glomerular filtration rate. ROC analysis further validates the diagnostic value of COL6A3, with the area under the ROC values of 0.879 in the in-house cohort, and 0.802 and 0.915 in tubular and glomerular external cohort samples, respectively. Furthermore, immunohistochemistry and qPCR experiments were consistent with those obtained from the single-cell RNA sequencing and proteomics studies. </p>Discussion<p>These results proved that COL6A3 is a promising biomarker and therapeutic target, advancing personalized medicine strategies for LN.</p>
eu_rights_str_mv openAccess
id Manara_b104faf7df85dabafe0ff035a00ee2be
identifier_str_mv 10.3389/fimmu.2024.1309447.s004
network_acronym_str Manara
network_name_str ManaraRepo
oai_identifier_str oai:figshare.com:article/27266652
publishDate 2024
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv CC BY 4.0
spelling Image1_Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics.tifLisha Mou (151003)Fan Zhang (46132)Xingjiao Liu (18608059)Ying Lu (66401)Mengli Yue (18608062)Yupeng Lai (12610630)Zuhui Pu (10931751)Xiaoyan Huang (112885)Meiying Wang (1309134)ImmunologyApplied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)AutoimmunityCellular ImmunologyHumoural Immunology and ImmunochemistryImmunogenetics (incl. Genetic Immunology)Innate ImmunityTransplantation ImmunologyTumour ImmunologyImmunology not elsewhere classifiedGenetic ImmunologyAnimal ImmunologyVeterinary Immunologysystemic lupus erythematosuskidney diseaselupus nephritissingle-cell RNA sequencingproteomicsCOL6A3biomarkersdiagnosisIntroduction<p>Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), presents significant challenges in patient management and treatment outcomes. The identification of novel LN-related biomarkers and therapeutic targets is critical to enhancing treatment outcomes and prognosis for patients.</p>Methods<p>In this study, we analyzed single-cell expression data from LN (n=21) and healthy controls (n=3). A total of 143 differentially expressed genes were identified between the LN and control groups. Then, proteomics analysis of LN patients (n=9) and control (SLE patients without LN, n=11) revealed 55 differentially expressed genes among patients with LN and control group. We further utilizes protein-protein interaction network and functional enrichment analyses to elucidate the pivotal role of COL6A3 in key signaling pathways. Its diagnostic value is evaluate through its correlation with disease progression and renal function metrics, as well as Receiver Operating Characteristic Curve (ROC) analysis. Additionally, immunohistochemistry and qPCR experiments were performed to validate the expression of COL6A3 in LN.</p>Results<p>By comparison of single-cell and proteomics data, we discovered that COL6A3 is significantly upregulated, highlighting it as a critical biomarker of LN. Our findings emphasize the substantial involvement of COL6A3 in the pathogenesis of LN, particularly noting its expression in mesangial cells. Through comprehensive protein-protein interaction network and functional enrichment analyses, we uncovered the pivotal role of COL6A3 in key signaling pathways including integrin-mediated signaling pathways, collagen-activated signaling pathways, and ECM-receptor interaction, suggesting potential therapeutic targets. The diagnostic utility is confirmed by its correlation with disease progression and renal function metrics of the glomerular filtration rate. ROC analysis further validates the diagnostic value of COL6A3, with the area under the ROC values of 0.879 in the in-house cohort, and 0.802 and 0.915 in tubular and glomerular external cohort samples, respectively. Furthermore, immunohistochemistry and qPCR experiments were consistent with those obtained from the single-cell RNA sequencing and proteomics studies. </p>Discussion<p>These results proved that COL6A3 is a promising biomarker and therapeutic target, advancing personalized medicine strategies for LN.</p>2024-10-21T08:15:35ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.3389/fimmu.2024.1309447.s004https://figshare.com/articles/figure/Image1_Integrative_analysis_of_COL6A3_in_lupus_nephritis_insights_from_single-cell_transcriptomics_and_proteomics_tif/27266652CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/272666522024-10-21T08:15:35Z
spellingShingle Image1_Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics.tif
Lisha Mou (151003)
Immunology
Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
Autoimmunity
Cellular Immunology
Humoural Immunology and Immunochemistry
Immunogenetics (incl. Genetic Immunology)
Innate Immunity
Transplantation Immunology
Tumour Immunology
Immunology not elsewhere classified
Genetic Immunology
Animal Immunology
Veterinary Immunology
systemic lupus erythematosus
kidney disease
lupus nephritis
single-cell RNA sequencing
proteomics
COL6A3
biomarkers
diagnosis
status_str publishedVersion
title Image1_Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics.tif
title_full Image1_Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics.tif
title_fullStr Image1_Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics.tif
title_full_unstemmed Image1_Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics.tif
title_short Image1_Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics.tif
title_sort Image1_Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics.tif
topic Immunology
Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
Autoimmunity
Cellular Immunology
Humoural Immunology and Immunochemistry
Immunogenetics (incl. Genetic Immunology)
Innate Immunity
Transplantation Immunology
Tumour Immunology
Immunology not elsewhere classified
Genetic Immunology
Animal Immunology
Veterinary Immunology
systemic lupus erythematosus
kidney disease
lupus nephritis
single-cell RNA sequencing
proteomics
COL6A3
biomarkers
diagnosis