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

Abstract Introduction 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). Methods Proteins were extracted from the saliva of three ESS and three normal con...

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Main Authors: Mingde Li, Yajun Qi, Guizhen Wang, Su Bu, Ming Chen, Jiahui Yu, Tianyang Luo, Lulu Meng, Anran Dai, Yong Zhou, Shuai Liu, Xingxing Huo
Format: Article
Language:English
Published: Wiley 2021-12-01
Series:Immunity, Inflammation and Disease
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Online Access:https://doi.org/10.1002/iid3.529
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author Mingde Li
Yajun Qi
Guizhen Wang
Su Bu
Ming Chen
Jiahui Yu
Tianyang Luo
Lulu Meng
Anran Dai
Yong Zhou
Shuai Liu
Xingxing Huo
author_facet Mingde Li
Yajun Qi
Guizhen Wang
Su Bu
Ming Chen
Jiahui Yu
Tianyang Luo
Lulu Meng
Anran Dai
Yong Zhou
Shuai Liu
Xingxing Huo
author_sort Mingde Li
collection DOAJ
description Abstract Introduction 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). Methods 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. Results 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. Conclusions 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.
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spelling doaj-art-07d0283d102244ef9846d8676a9ffccb2025-08-20T02:46:35ZengWileyImmunity, Inflammation and Disease2050-45272021-12-01941724173910.1002/iid3.529Proteomic profiling of saliva reveals association of complement system with primary Sjögren's syndromeMingde Li0Yajun Qi1Guizhen Wang2Su Bu3Ming Chen4Jiahui Yu5Tianyang Luo6Lulu Meng7Anran Dai8Yong Zhou9Shuai Liu10Xingxing Huo11Experimental Center of Clinical Research, Scientific Research Department The First Affiliated Hospital of Anhui University of Chinese Medicine Hefei Anhui ChinaDepartment of Traditional Chinese Medicine, College of Acupuncture and Massage Anhui University of traditional Chinese Medicine Hefei Anhui ChinaDepartment of Rheumatology The First Affiliated Hospital of Anhui University of Chinese Medicine Hefei ChinaExperimental Center of Clinical Research, Scientific Research Department The First Affiliated Hospital of Anhui University of Chinese Medicine Hefei Anhui ChinaDepartment of Anesthesiology, Second Clinical Medical College Anhui Medical University Hefei Anhui ChinaDepartment of Traditional Chinese Pharmacology, College of Pharmacy Anhui Medical University Hefei Anhui ChinaDepartment of Anesthesiology, Second Clinical Medical College Anhui Medical University Hefei Anhui ChinaExperimental Center of Clinical Research, Scientific Research Department The First Affiliated Hospital of Anhui University of Chinese Medicine Hefei Anhui ChinaExperimental Center of Clinical Research, Scientific Research Department The First Affiliated Hospital of Anhui University of Chinese Medicine Hefei Anhui ChinaExperimental Center of Clinical Research, Scientific Research Department The First Affiliated Hospital of Anhui University of Chinese Medicine Hefei Anhui ChinaExperimental Center of Clinical Research, Scientific Research Department The First Affiliated Hospital of Anhui University of Chinese Medicine Hefei Anhui ChinaExperimental Center of Clinical Research, Scientific Research Department The First Affiliated Hospital of Anhui University of Chinese Medicine Hefei Anhui ChinaAbstract Introduction 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). Methods 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. Results 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. Conclusions 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.https://doi.org/10.1002/iid3.529biomarkersdifferentially expressed proteinsprimary Sjögren's syndromesalivary proteomic
spellingShingle Mingde Li
Yajun Qi
Guizhen Wang
Su Bu
Ming Chen
Jiahui Yu
Tianyang Luo
Lulu Meng
Anran Dai
Yong Zhou
Shuai Liu
Xingxing Huo
Proteomic profiling of saliva reveals association of complement system with primary Sjögren's syndrome
Immunity, Inflammation and Disease
biomarkers
differentially expressed proteins
primary Sjögren's syndrome
salivary proteomic
title Proteomic profiling of saliva reveals association of complement system with primary Sjögren's syndrome
title_full Proteomic profiling of saliva reveals association of complement system with primary Sjögren's syndrome
title_fullStr Proteomic profiling of saliva reveals association of complement system with primary Sjögren's syndrome
title_full_unstemmed Proteomic profiling of saliva reveals association of complement system with primary Sjögren's syndrome
title_short Proteomic profiling of saliva reveals association of complement system with primary Sjögren's syndrome
title_sort proteomic profiling of saliva reveals association of complement system with primary sjogren s syndrome
topic biomarkers
differentially expressed proteins
primary Sjögren's syndrome
salivary proteomic
url https://doi.org/10.1002/iid3.529
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