Abstract
Purpose
The mechanisms underlying HBV intrauterine transmission remain unknown. In this study, we explored the mechanism of HBV intrauterine transmission by iTRAQ proteomics analysis.
Methods
iTRAQ technology was applied to perform comparative proteomics studies on six HBV+/+ neonates and six HBV+/− neonates whose mothers and fathers were HBsAg positive and paternal HBsAg negative, respectively. The data obtained from the mass spectrometer were analyzed using MASCOT (https://matrixscience.com) to qualitatively and quantitatively compare the differentially expressed proteins in the two groups. Gene Ontology and KEGG pathway analyses were performed to analyze the differentially expressed proteins. The expressions of HBV intrauterine transmission-related proteins in serum samples and corresponding placental tissues were further verified by immunohistochemistry and Western Blot. Then, the human trophoblast cell line (Swan71) infected with HBV was used to analyze the potential mechanisms of HBV intrauterine transmission under the mediation of differential proteins.
Results
A total of 35 differentially expressed proteins, including 17 up-regulated proteins and 18 down-regulated proteins, were identified by comparing serum protein expression levels in HBV+/+ and HBV+/− neonates. The differentially expressed proteins were mainly related to RAGE receptor binding, NF-kappa B transcription factor activity, innate immune response, defense response to bacterium, and the signaling pathway in pathogenic microorganism infection. The expressions of S100A8/9/12 in HBV+/+ maternal placenta tissue were significantly increased. The expressions of S100A8/9/12 proteins in Swan71 cells were significantly increased after HBV infection.
Conclusion
High expression of S100 proteins may be associated with the intrauterine-transplacental transmission of HBV.
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Availability of data and materials
The analyzed data sets generated during the study are available from the corresponding author on reasonable request.
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Funding
This work was supported by the National Natural Science Foundation of China [81671478]; the Health and Family Planning Commission of Zhejiang Province of China [2017KY904].
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Substantial contributions to conception and design: PZ, JW; data acquisition, data analysis and interpretation: LQ, XZ, XB, HW; drafting the article or critically revising it for important intellectual content: PZ, JW; final approval of the version to be published: All authors. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved: all authors.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animals are involved in this research.
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Zhao, P., Wen, J., Qian, L. et al. Expression of S100 proteins is associated with HBV intrauterine transmission. Arch Gynecol Obstet 302, 1389–1399 (2020). https://doi.org/10.1007/s00404-020-05753-6
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DOI: https://doi.org/10.1007/s00404-020-05753-6