A proteomics analysis reveals that A2M might be regulated by STAT3 in persistent allergic rhinitis

蛋白质组学分析表明,在持续性过敏性鼻炎中,A2M 可能受 STAT3 调控

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作者:X Chen, Z H Xie, Y X Lv, Q P Tang, H Zhang, J Y Zhang, B Wu, W H Jiang

Background

Proteomics tools can be used to identify the differentially expressed proteins related to allergic rhinitis (AR). However, the large numbers of proteins related to AR have not yet been explored using an advanced quantitative proteomics approach, known as isobaric tags for relative and absolute quantitation (iTRAQ). Objectives: To identify differentially expressed proteins in persistent AR patients and to explore the regulatory signalling pathways involving the identified proteins.

Conclusions

The blood coagulation pathway may be a key regulatory network pathway contributing to the allergic inflammatory response in AR patients. A2M, which is regulated by STAT3, may be an important protein in the pathogenesis of allergic rhinitis in AR patients.

Methods

Forty-five persistent AR patients and 20 healthy controls were recruited for this study. iTRAQ was used to identify the proteins that were differentially expressed between these two groups, and a bioinformatics analysis was then conducted to identify the signalling pathways associated with the identified proteins. Immunofluorescence labelling was performed to detect alpha-2-macroglobulin (A2M), STAT3, p-STAT3 and IL17 in the nasal mucosa.

Results

A total of 133 differentially expressed proteins were identified. We then determined the top 10 regulatory pathways associated with these proteins and found that the blood coagulation pathway had the most significant association. A2M, a protein involved in the blood coagulation pathway, was found to be differentially expressed in the serum of AR patients. The bioinformatics analysis indicated that STAT3 is an upstream transcription factor that might regulate A2M expression. An immunofluorescence study further confirmed that STAT3 and A2M are co-localized in nasal mucosa cells. Additionally, A2M, STAT3, p-STAT3, and IL17 are elevated in AR patients. The expressional level of A2M is positively related to IL17 and the symptom of the congestion in AR subjects. Conclusions: The blood coagulation pathway may be a key regulatory network pathway contributing to the allergic inflammatory response in AR patients. A2M, which is regulated by STAT3, may be an important protein in the pathogenesis of allergic rhinitis in AR patients.

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