Expression of S100 proteins is associated with HBV intrauterine transmission

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GENERAL GYNECOLOGY

Expression of S100 proteins is associated with HBV intrauterine transmission Peng Zhao1 · Jie Wen1 · Linyan Qian1 · Xiaojun Zhu1 · Hong Wang1 · Xiaoxia Bai1  Received: 20 April 2020 / Accepted: 15 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

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​://matri​xscie​nce.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 H ­ BV+/+  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 H ­ BV+/+ 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. Keywords  Hepatitis B virus · Placenta · Intrauterine transmission

Introduction Hepatitis B virus (HBV) infection is one of the major global health issues. According to WHO, about 2 billion people worldwide have been infected with HBV, of whom 248 million have developed into chronic hepatitis B virus carriers Peng Zhao and Jie Wen contributed equally to this work. * Jie Wen [email protected] * Xiaoxia Bai [email protected] 1



Department of Obstetrics, Women’s Hospital, Medical School of Zhejiang University, No. 1 Xueshi Road, Shangcheng District, Hangzhou 310006, Zhejiang Province, China

[1]. Meanwhile, about 1 million people die of chronic HBV infection-related cirrhosis, liver failure, and primary hepatocellular carcinoma each year. Hepatitis B infection is highly prevalent in China, and the HBV carrier rate of the population is as high as 10% [2]. Studies have confir