Molecular mechanism of high altitude hypoxia-induced PLCG2 expression inhibition: a study based on ubiquitination modification omics study

Chen Xiaochen; Li Jidong; Wang Xiaojun; Hu Ying; Xu Yuzhen; Yong Sheng

doi:10.13406/j.cnki.cyxb.003779

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Molecular mechanism of high altitude hypoxia-induced PLCG2 expression inhibition: a study based on ubiquitination modification omics study

Basic research | 更新时间：2026-02-13

- Molecular mechanism of high altitude hypoxia-induced PLCG2 expression inhibition: a study based on ubiquitination modification omics study
- Journal of Chongqing Medical University Vol. 51, Issue 1, Pages: 84-92(2026)
- 作者机构：
  
  青海大学医学院基础医学部，西宁 810016
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003779
  CLC： R392.1
- Received：24 July 2024，
  
  Revised：2024-10-21，
  
  Published：28 January 2026
- 稿件说明：
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陈晓晨,李积东,汪晓筠等.基于泛素化修饰组学研究高原低氧抑制PLCG2表达的分子机制[J].重庆医科大学学报,2026,51(01):84-92.

Chen Xiaochen,Li Jidong,Wang Xiaojun,et al.Molecular mechanism of high altitude hypoxia-induced PLCG2 expression inhibition: a study based on ubiquitination modification omics study[J].Journal of Chongqing Medical University,2026,51(01):84-92.
陈晓晨,李积东,汪晓筠等.基于泛素化修饰组学研究高原低氧抑制PLCG2表达的分子机制[J].重庆医科大学学报,2026,51(01):84-92. DOI： 10.13406/j.cnki.cyxb.003779.

Chen Xiaochen,Li Jidong,Wang Xiaojun,et al.Molecular mechanism of high altitude hypoxia-induced PLCG2 expression inhibition: a study based on ubiquitination modification omics study[J].Journal of Chongqing Medical University,2026,51(01):84-92. DOI： 10.13406/j.cnki.cyxb.003779.

摘要

目的

利用泛素化修饰组学探究低氧暴露导致小鼠脾脏组织蛋白质表达水平的变化，阐明高原低氧环境对小鼠脾脏免疫炎症反应的影响机制。

方法

将C57BL/6小鼠分别置于400 m和4 200 m的海拔饲养，30 d 后无菌取出脾脏进行泛素化修饰组学研究，通过鉴定泛素化蛋白质、泛素化肽段、泛素化位点，分析差异表达泛素化肽段并进行生物信息学分析。

结果

泛素化修饰组学共鉴定到的泛素化蛋白质、泛素化肽段、泛素化位点的数目分别为1 457、2 982、3 373，其中1 100个修饰蛋白上有2 089条可定量泛素化肽段，2 255个可定量泛素化位点。在显著性差异修饰肽段筛选中共鉴定出69个差异表达泛素化肽段，其中46个修饰肽段表达上调，23个修饰肽段表达下调。通过对差异表达泛素化肽段对应的蛋白质做GO功能注释分析发现高原低氧组中差异表达蛋白质多与细胞进程、生物调节和免疫过程等相关，京都基因与基因组百科全书（kyoto encyclopedia of g

enes and genomes，KEGG）通路富集分析发现差异表达蛋白质显著富集到丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）信号通路、RAS基因家族（rat sarcoma viral oncogene homolog，RAS）信号通路和神经内分泌肿瘤（neuroendocrine tumor，NET）信号通路中，因此对通路中关键蛋白进行验证，发现磷脂酶Cγ2（phospholipase Cγ2，PLCG2）蛋白表达显著下调（

=0.022），血小板衍生生长因子受体α（platelet derived growth factor receptor，alpha polypeptide，PDGFRA）蛋白表达水平上调（

=0.045）、磷脂酶A2 IVA组（phospholipase A2 group IVA，PLA2G4A）蛋白表达水平显著上调（

=0.015）；炎症因子白细胞介素（interleukin，IL）-1β（

=0.009）、IL-6（

0.001）、IL-12（

=0.014）和肿瘤坏死因子-α（tumor necrosis factor-alpha，TNF-α）（

0.001）的mRNA表达量显著上调。

结论

通过泛素化修饰组学分析低氧暴露导致小鼠脾脏组织中蛋白表达差异的分子机制，借助生物信息学分析，发现高原低氧环境可通过改变MAPK信号通路、RAS信号通路和NET信号通路中蛋白修饰水平，抑制小鼠脾脏组织中PLCG2的表达，进而导致机体免疫系统功能障碍以及炎症反应的发生。

Abstract

Objective

To explore the changes in protein expression levels in mouse spleen tissues caused by hypoxic exposure using ubiquitination modification omics，and to elucidate the mechanism of the impact of high altitude hypoxia environment on immune inflammatory response in the mouse spleen.

Methods

C57BL/6 mice were raised at an altitude of 400 m and 4 200 m，respectively. After 30 days，the spleen was removed aseptically for ubiquitination modification omics study. By identifying ubiquitinated proteins，ubiquitinated peptides，and ubiquitinated sites，the differentially expressed ubiquitinated peptides were analyzed，and bioinformatics analysis was conducted.

Results

The total counts of ubiquitinated proteins，ubiquitinated peptides，and ubiquitinated sites identified by ubiquitination modification omics were 1 457，2 982，and 3 373，respectively. There were 2 089 quantifiable ubiquitinated peptides and 2 255 quantifiable ubiquitinated sites identified across 1 100 modified proteins. A total of 69 differentially expressed ubiquitinated peptides

were detected during the screening for significantly differentially modified peptides，of which，46 modified peptides exhibited up-regulated expression and 23 modified peptides showed down-regulated expression. The gene ontology functional annotation analysis on proteins corresponding to the differentially expressed ubiquitinated peptides revealed that the differentially expressed proteins in the high altitude hypoxia group predominantly involved in the cellular process，biological regulation，and immune response. The KEGG pathway enrichment analysis indicated significant enrichment of differentially expressed proteins within MAPK signaling pathway，RAS signaling pathway，and NET formation pathway. Consequently，validation of key proteins in these pathways revealed that platelet derived growth factor receptor，alpha polypeptide（PDGFRA）（

=0.045） and （phospholipase A2 group IVA，PLA2G4A）（

=0.015） protein expression levels were significantly up-regulated，while （phospholipase Cγ2，PLCG2）（

=0.022） protein expression level was significantly down-regulated；the mRNA expression levels of inflammatory factors interleukin（IL）-1β（

=0.009），IL-6（

0.001），IL-12（

=0.014），and tumor necrosis factor-α（

0.001） were significantly up-regulated.

Conclusion

The ubiquitination modification omics analysis，with the aid of bioinformatics analysis，found that high altitude hypoxia environment inhibits the expression of PLCG2 in the mouse spleen by changing the protein modification levels in MAPK signaling pathway，RAS signaling pathway，and NET formation pathway. This in turn leads to dysfunction of the body’s immune system and inflammation.

关键词

Keywords

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