Opposing roles of inter-α-trypsin inhibitor heavy chain 4 in recurrent pregnancy loss
| Autor: | Jinyoung Paek, Sang-Jin Song, Chang-Zhu Pei, Lan Li, Kwang-Hyun Baek, Bum-Chae Choi, Ji Eun Ryoo, Kwang Yul Lee |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
0301 basic medicine Abortion Habitual Research paper Proteinase Inhibitory Proteins Secretory Early pregnancy loss Inflammation Biology Peripheral blood mononuclear cell Monocytes ITI-H4 General Biochemistry Genetics and Molecular Biology Immune tolerance Pathogenesis 03 medical and health sciences Immune system Cell Movement Pregnancy Risk Factors medicine Humans Migration and invasion Cell Proliferation Glycoproteins Interleukin-6 Trophoblast Blood Proteins General Medicine Kallikrein Plasma kallikrein Trophoblasts 030104 developmental biology medicine.anatomical_structure Cancer research Biomarker (medicine) Female medicine.symptom Biomarkers Signal Transduction |
| Zdroj: | EBioMedicine |
| ISSN: | 2352-3964 |
| Popis: | Background The mechanism behind an increased risk of recurrent pregnancy loss (RPL) remains largely unknown. In our previous study, we identified that inter-α-trypsin inhibitor heavy chain 4 (ITI-H4) is highly expressed at a modified molecular weight of 36 kDa in serum derived from RPL patients. Yet, the precise molecular mechanism and pathways by which the short form of ITI-H4 carries out its function remain obscure. Methods Human sera and peripheral blood mononucleated cells (PBMCs) were collected from patients and normal controls to compare the expression levels of ITI-H4 and plasma kallikrein (KLKB1). Flow cytometric assay was performed to measure inflammatory markers in sera and culture supernatants. Furthermore, to investigate the functions of the two isoforms of ITI-H4, we performed migration, invasion, and proliferation assays. Findings In the current study, we showed that ITI-H4 as a biomarker of RPL could be regulated by KLKB1 through the IL-6 signaling cascade, indicating a novel regulatory system for inflammation in RPL. In addition, our study indicates that the two isoforms of ITI-H4 possess opposing functions on immune response, trophoblast invasion, and monocytes migration or proliferation. Interpretation The ITI-H4 (∆N688) might be a crucial inflammatory factor which contributes to the pathogenesis of RPL. Moreover, it is expected that this study would give some insights into potential functional mechanisms underlying RPL. Fund This study was supported by the Ministry of Health & Welfare of the Republic of Korea (HI18C0378) through the Korea Health Industry Development Institute. Graphical abstract Unlabelled Image |
| Databáze: | OpenAIRE |
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