Evidence map›Paper›PMID 34073978›Full record

ArticleCells2021

Extracellularly Released Calreticulin Induced by Endoplasmic Reticulum Stress Impairs Syncytialization of Cytotrophoblast Model BeWo Cells.

Naoyuki Iwahashi, Midori Ikezaki, Kazuchika Nishitsuji, Madoka Yamamoto, Ibu Matsuzaki, Naoki Kato, Naoyuki Takaoka, Mana Taniguchi, Shin-Ichi Murata, Kazuhiko Ino and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 25 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Naoyuki IwahashiDepartment of Obstetrics and Gynecology, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-8509, Japan.ORCID 0000-0002-6422-325X
Midori IkezakiDepartment of Biochemistry, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-8509, Japan.ORCID 0000-0003-3629-3629
Kazuchika NishitsujiDepartment of Biochemistry, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-8509, Japan.ORCID 0000-0003-3056-8310
Madoka YamamotoDepartment of Obstetrics and Gynecology, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-8509, Japan.
Ibu MatsuzakiDepartment of Human Pathology, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-8509, Japan.
Naoki KatoDepartment of Biochemistry, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-8509, Japan.
Naoyuki TakaokaDepartment of Biochemistry, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-8509, Japan.
Mana TaniguchiDepartment of Biochemistry, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-8509, Japan.
Shin-Ichi MurataDepartment of Human Pathology, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-8509, Japan.
Kazuhiko InoDepartment of Obstetrics and Gynecology, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-8509, Japan.
Yoshito IharaDepartment of Biochemistry, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-8509, Japan.ORCID 0000-0002-8674-5681
Wakayama Medical University · JP

Funding

Japan Society for the Promotion of Science 18K16809Japan Society for the Promotion of Science 19K09784Japan Society for the Promotion of Science 20K18228Japan Society for the Promotion of Science JP18K16776the Japan Society for the Study of Hypertension in Pregnancy 2019Wakayama Medical University Tokutei-kenkyu-zyosei 2019Wakayama Medical University Tokutei-kenkyu-zyosei 2020
6 · The paper itself

Abstract

The pregnancy-specific syndrome preeclampsia is a major cause of maternal mortality throughout the world. The initial insult resulting in the development of preeclampsia is inadequate trophoblast invasion, which may lead to reduced maternal perfusion of the placenta and placental dysfunction, such as insufficient trophoblast syncytialization. Endoplasmic reticulum (ER) stress has been implicated in the pathology of preeclampsia and serves as the major risk factor. Our previous studies suggested critical roles of calreticulin (CRT), which is an ER-resident stress response protein, in extravillous trophoblast invasion and cytotrophoblast syncytialization. Here, we studied the mechanism by which ER stress exposes the placenta to the risk of preeclampsia. We found that CRT was upregulated in the serum samples, but not in the placental specimens, from preeclamptic women. By using BeWo cells, an established model of cytotrophoblasts that syncytialize in the presence of forskolin, we demonstrated that thapsigargin-induced ER stress caused extracellular release of CRT from BeWo cells and that the extracellular CRT suppressed forskolin-induced release of β-human chorionic gonadotropin and altered subcellular localization of E-cadherin, which is a key adhesion molecule associated with syncytialization. Our results together provide evidence that induction of ER stress leads to extracellular CRT release, which may contribute to placental dysfunction by suppressing cytotrophoblast syncytialization.

Indexed as

Endoplasmic Reticulum StressCalreticulinCell LineGiant CellsHumansTrophoblastsCalreticulinCALR protein, humancalreticulinendoplasmic reticulum stresspreeclampsiasyncytializationtrophoblast

Identifiers

PMID34073978
PMCPMC8225044
OpenAlexW3164145337

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.