Pathological mechanisms of type 1 diabetes in children: investigation of the exosomal protein expression profile
IntroductionType 1 diabetes (T1D) is a serious autoimmune disease with high morbidity and mortality. Early diagnosis and treatment remain unsatisfactory. While the potential for development of T1D biomarkers in circulating exosomes has attracted interest, progress has been limited. This study endeav...
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Frontiers Media S.A.
2023-10-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1271929/full |
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author | Baoling Bai Kang Gao Kexin Zhang Lingyun Liu Xiaobo Chen Qin Zhang |
author_facet | Baoling Bai Kang Gao Kexin Zhang Lingyun Liu Xiaobo Chen Qin Zhang |
author_sort | Baoling Bai |
collection | DOAJ |
description | IntroductionType 1 diabetes (T1D) is a serious autoimmune disease with high morbidity and mortality. Early diagnosis and treatment remain unsatisfactory. While the potential for development of T1D biomarkers in circulating exosomes has attracted interest, progress has been limited. This study endeavors to explore the molecular dynamics of plasma exosome proteins in pediatric T1D patients and potential mechanisms correlated with T1D progressionMethodsLiquid chromatography-tandem mass spectrometry with tandem mass tag (TMT)6 labeling was used to quantify exosomal protein expression profiles in 12 healthy controls and 24 T1D patients stratified by age (≤ 6 years old and > 6 years old) and glycated hemoglobin (HbA1c) levels (> 7% or > 7%). Integrated bioinformatics analysis was employed to decipher the functions of differentially expressed proteins, and Western blotting was used for validation of selected proteins' expression levels. ResultsWe identified 1035 differentially expressed proteins (fold change > 1.3) between the T1D patients and healthy controls: 558 in those ≤ 6-year-old and 588 in those > 6-year-old. In those who reached an HbA1c level < 7% following 3 or more months of insulin therapy, the expression levels of most altered proteins in both T1D age groups returned to levels comparable to those in the healthy control group. Bioinformatics analysis revealed that differentially expressed exosome proteins are primarily related to immune function, hemostasis, cellular stress responses, and matrix organization. Western blotting confirmed the alterations in RAB40A, SEMA6D, COL6A5, and TTR proteins. DiscussionThis study delivers valuable insights into the fundamental molecular mechanisms contributing to T1D pathology. Moreover, it proposes potential therapeutic targets for improved T1D management. |
first_indexed | 2024-03-11T18:52:47Z |
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id | doaj.art-91c9e2f438ed448e8d90df0ff167f90f |
institution | Directory Open Access Journal |
issn | 1664-2392 |
language | English |
last_indexed | 2024-03-11T18:52:47Z |
publishDate | 2023-10-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Endocrinology |
spelling | doaj.art-91c9e2f438ed448e8d90df0ff167f90f2023-10-11T07:44:29ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-10-011410.3389/fendo.2023.12719291271929Pathological mechanisms of type 1 diabetes in children: investigation of the exosomal protein expression profileBaoling Bai0Kang Gao1Kexin Zhang2Lingyun Liu3Xiaobo Chen4Qin Zhang5Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, ChinaEndocrinology Department, Children’s Hospital of Capital Institute of Pediatrics, Beijing, ChinaBeijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, ChinaBeijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, ChinaEndocrinology Department, Children’s Hospital of Capital Institute of Pediatrics, Beijing, ChinaBeijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, ChinaIntroductionType 1 diabetes (T1D) is a serious autoimmune disease with high morbidity and mortality. Early diagnosis and treatment remain unsatisfactory. While the potential for development of T1D biomarkers in circulating exosomes has attracted interest, progress has been limited. This study endeavors to explore the molecular dynamics of plasma exosome proteins in pediatric T1D patients and potential mechanisms correlated with T1D progressionMethodsLiquid chromatography-tandem mass spectrometry with tandem mass tag (TMT)6 labeling was used to quantify exosomal protein expression profiles in 12 healthy controls and 24 T1D patients stratified by age (≤ 6 years old and > 6 years old) and glycated hemoglobin (HbA1c) levels (> 7% or > 7%). Integrated bioinformatics analysis was employed to decipher the functions of differentially expressed proteins, and Western blotting was used for validation of selected proteins' expression levels. ResultsWe identified 1035 differentially expressed proteins (fold change > 1.3) between the T1D patients and healthy controls: 558 in those ≤ 6-year-old and 588 in those > 6-year-old. In those who reached an HbA1c level < 7% following 3 or more months of insulin therapy, the expression levels of most altered proteins in both T1D age groups returned to levels comparable to those in the healthy control group. Bioinformatics analysis revealed that differentially expressed exosome proteins are primarily related to immune function, hemostasis, cellular stress responses, and matrix organization. Western blotting confirmed the alterations in RAB40A, SEMA6D, COL6A5, and TTR proteins. DiscussionThis study delivers valuable insights into the fundamental molecular mechanisms contributing to T1D pathology. Moreover, it proposes potential therapeutic targets for improved T1D management.https://www.frontiersin.org/articles/10.3389/fendo.2023.1271929/fulltype 1 diabetesexosomeproteomicsTMT6insulin treatment |
spellingShingle | Baoling Bai Kang Gao Kexin Zhang Lingyun Liu Xiaobo Chen Qin Zhang Pathological mechanisms of type 1 diabetes in children: investigation of the exosomal protein expression profile Frontiers in Endocrinology type 1 diabetes exosome proteomics TMT6 insulin treatment |
title | Pathological mechanisms of type 1 diabetes in children: investigation of the exosomal protein expression profile |
title_full | Pathological mechanisms of type 1 diabetes in children: investigation of the exosomal protein expression profile |
title_fullStr | Pathological mechanisms of type 1 diabetes in children: investigation of the exosomal protein expression profile |
title_full_unstemmed | Pathological mechanisms of type 1 diabetes in children: investigation of the exosomal protein expression profile |
title_short | Pathological mechanisms of type 1 diabetes in children: investigation of the exosomal protein expression profile |
title_sort | pathological mechanisms of type 1 diabetes in children investigation of the exosomal protein expression profile |
topic | type 1 diabetes exosome proteomics TMT6 insulin treatment |
url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1271929/full |
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