Altered exosomal protein expression in the serum of NF-κB knockout mice following skeletal muscle ischemia-reperfusion injury

Journal of Biomedical Science

Ching-Hua Hsieh²  Chia-Jung Wu²  Siou-Ling Tzeng²  Yi-Chun Chen²  Yi-Chan Wu²  Tsu-Hsiang Lu²  Seng-Feng Jeng³  Cheng-Shyuan Rau¹  Ming-Wei Lin²  Johnson Chia-Shen Yang² 

[1] Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, Taiwan;Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niao-Sung District, Kaohsiung City 833, Taiwan;Department of Plastic Surgery, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan

关键词: Proteomics;    Two-dimensional-gel electrophoresis;    NF-κB;    Exosome;    Muscle ischemia-reperfusion (I/R) injury;   

Others  :  1213943
DOI  :  10.1186/s12929-015-0147-x

 received in 2014-12-16, accepted in 2015-05-15,  发布年份 2015

【 摘 要 】

Background

The NF-κB signaling pathway plays a role in local and remote tissue damage following ischemia-reperfusion (I/R) injury to skeletal muscles. Evidence suggests that exosomes can act as intercellular communicators by transporting active proteins to remote cells and may play a role in regulating inflammatory processes. This study aimed to profile the exosomal protein expression in the serum of NF-κB knockout mice following skeletal muscle ischemia-reperfusion injury.

Results

To investigate the potential changes in protein expression mediated by NF-κB in secreted exosomes in the serum following I/R injury, the levels of circulating exosomal proteomes in C57BL/6 and NF-κB^−/− mice were compared using two dimensional differential in-gel electrophoresis (2-DE), liquid chromatography tandem mass spectrometry (LC-MS/MS), and proteomic analysis. In C57BL/6 mice, the levels of circulating exosomal proteins, including complement component C3 prepropeptide, PK-120 precursor, alpha-amylase one precursor, beta-enolase isoform 1, and adenylosuccinate synthetase isozyme 1, increased following I/R injury. However, in the NF-κB^−/− mice, the expression of the following was upregulated in the exosomes: protease, serine 1; glyceraldehyde-3-phosphate dehydrogenase-like isoform 1; glyceraldehyde-3-phosphate dehydrogenase; and pregnancy zone protein. In contrast, the expression of apolipoprotein B, complement component C3 prepropeptide, and immunoglobulin kappa light chain variable region was downregulated in NF-κB^−/− mice. Bioinformatic annotation using the Protein Analysis Through Evolutionary Relationships (PANTHER) database revealed that the expression of the exosomal proteins that participate in metabolic processes and in biological regulation was lower in NF-κB^−/− mice than in C57BL/6 mice, whereas the expression of proteins that participate in the response to stimuli, in cellular processes, and in the immune system was higher.

Conclusions

The data presented in this study suggest that NF-κB might regulate exosomal protein expression at a remote site via circulation following I/R injury.

【 授权许可】

   
2015 Yang et al.

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