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Opposing roles of inter-?-trypsin inhibitor heavy chain 4 in recurrent pregnancy loss.


ABSTRACT:

Background

The mechanism behind an increased risk of recurrent pregnancy loss (RPL) remains largely unknown. In our previous study, we identified that inter-?-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.

SUBMITTER: Li L 

PROVIDER: S-EPMC6286651 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Opposing roles of inter-α-trypsin inhibitor heavy chain 4 in recurrent pregnancy loss.

Li Lan L   Choi Bum-Chae BC   Ryoo Ji Eun JE   Song Sang-Jin SJ   Pei Chang-Zhu CZ   Lee Kwang Yul KY   Paek Jinyoung J   Baek Kwang-Hyun KH  

EBioMedicine 20181019


<h4>Background</h4>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.<h4>Methods</h4>Human sera and peripheral blood mononucleated cells (PB  ...[more]

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