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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Main Authors: Baoling Bai, Kang Gao, Kexin Zhang, Lingyun Liu, Xiaobo Chen, Qin Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-10-01
Series:Frontiers in Endocrinology
Subjects:
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.
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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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