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川崎病小鼠模型心脏中蛋白质的赖氨酸乳酰化分析

Lysine lactylation analysis of proteins in the heart of the Kawasaki disease mouse model.

作者信息

Zhuo Wenyu, Zhang Mingyang, Tan Jiajia, Gao Yang, Wang Yan, Wang Nana, Ma Jin, Zhang Jiaying, Liu Zhiheng, Lv Haitao, Liu Ying

机构信息

Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu, China.

Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China.

出版信息

Front Cell Dev Biol. 2025 Mar 6;13:1550220. doi: 10.3389/fcell.2025.1550220. eCollection 2025.

DOI:10.3389/fcell.2025.1550220
PMID:40114965
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11922914/
Abstract

INTRODUCTION

Kawasaki disease (KD) is a medium-vessel vasculitis predominantly affecting children under 5 years of age and may involve the coronary arteries.

METHODS

A mouse KD model was induced by cell wall extracts (CAWS), cardiac tissues were analyzed through integrated lactylomic and proteomic profiling. The lysine lactylation (Kla) results were normalized to the proteomic data.

RESULTS

Elevated serum lactate and lactate dehydrogenase (LDH) levels were observed in KD patients. Given lactate's role as a substrate for Kla, this study investigated Kla modifications in KD. Proteomic analysis identified 150 upregulated proteins and 18 downregulated proteins, with 38.1% located in the cytoplasm and significant enrichment in immune-related pathways. After normalization, 41 sites in 37 proteins were found to be upregulated in the Kla data, with no downregulated sites. Approximately 67.57% of the altered proteins were localized in the mitochondria. Bioinformatics analysis indicated alterations in aerobic respiration, energy production and conversion, and key immune- and metabolism-related pathways.

DISCUSSION

This study enhances the understanding of Kla modifications in the development of KD and may inform targeted therapies for its prevention and improved prognosis.

摘要

引言

川崎病(KD)是一种主要影响5岁以下儿童的中血管血管炎,可能累及冠状动脉。

方法

通过细胞壁提取物(CAWS)诱导建立小鼠KD模型,通过综合乳酸化蛋白质组学分析对心脏组织进行分析。将赖氨酸乳酸化(Kla)结果与蛋白质组数据进行归一化处理。

结果

在KD患者中观察到血清乳酸和乳酸脱氢酶(LDH)水平升高。鉴于乳酸作为Kla底物的作用,本研究调查了KD中的Kla修饰。蛋白质组分析鉴定出150种上调蛋白和18种下调蛋白,其中38.1%位于细胞质中,且在免疫相关途径中显著富集。归一化后,在Kla数据中发现37种蛋白质的41个位点上调,无下调位点。约67.57%的改变蛋白定位于线粒体。生物信息学分析表明有氧呼吸、能量产生和转换以及关键免疫和代谢相关途径发生了改变。

讨论

本研究增进了对KD发展过程中Kla修饰的理解,并可能为其预防和改善预后的靶向治疗提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/417b/11922914/e51658d2fcdc/fcell-13-1550220-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/417b/11922914/ae1e700adcde/fcell-13-1550220-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/417b/11922914/aa56739ea242/fcell-13-1550220-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/417b/11922914/0eee2f6c5685/fcell-13-1550220-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/417b/11922914/e51658d2fcdc/fcell-13-1550220-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/417b/11922914/ae1e700adcde/fcell-13-1550220-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/417b/11922914/aa56739ea242/fcell-13-1550220-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/417b/11922914/0eee2f6c5685/fcell-13-1550220-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/417b/11922914/e51658d2fcdc/fcell-13-1550220-g004.jpg

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