Evidence map›Paper›PMID 35607996›Full record

ArticleHypertension (Dallas, Tex. : 1979)2022

Evidence From Human Placenta, Endoplasmic Reticulum-Stressed Trophoblasts, and Transgenic Mice Links Transthyretin Proteinopathy to Preeclampsia.

Shibin Cheng, Zheping Huang, Sayani Banerjee, Sukanta Jash, Joel N Buxbaum, Surendra Sharma

Open access · bronzeAbstract read
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

17 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

6 authors at 2 institutions in 1 country.

Shibin ChengDepartment of Pediatrics, Women & Infants Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.C., Z.H., S.B., S.J., S.S.).
Zheping HuangDepartment of Pediatrics, Women & Infants Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.C., Z.H., S.B., S.J., S.S.).ORCID 0000-0002-2242-5216
Sayani BanerjeeDepartment of Pediatrics, Women & Infants Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.C., Z.H., S.B., S.J., S.S.).
Sukanta JashDepartment of Pediatrics, Women & Infants Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.C., Z.H., S.B., S.J., S.S.).
Joel N BuxbaumDepartment of Molecular Medicine, Scripps Research Institute, La Jolla, CA (J.N.B.).
Surendra SharmaDepartment of Pediatrics, Women & Infants Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.C., Z.H., S.B., S.J., S.S.).
Brown University · USScripps Research Institute · US

Funding

Transcriptional Profiling of Exosomes Defines Molecular Phenotype of PreclampsiaP20GM121298 · NIGMS · WOMEN AND INFANTS HOSPITAL-RHODE ISLAND · PI SHARMA, SURENDRA · 2017 to 2021
$12.6M
Research CoreP30GM114750 · NIGMS · WOMEN AND INFANTS HOSPITAL-RHODE ISLAND · PI SHAW, SUNIL K · 2015 to 2019
$4.5M
Aging and the Tissue Response to Misfolded ProteinsR01AG030027 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI BUXBAUM, JOEL N · 2008 to 2012
$2.1M
NIA NIH HHS R01 AG030027NIGMS NIH HHS P20 GM121298NIGMS NIH HHS P30 GM114750
6 · The paper itself

Abstract

backgroundWe have demonstrated that protein aggregation plays a pivotal role in the pathophysiology of preeclampsia and identified several aggregated proteins in the circulation of preeclampsia patients, the most prominent of which is the serum protein TTR (transthyretin). However, the mechanisms that underlie protein aggregation remain poorly addressed.

methodsWe examined TTR aggregates in hypoxia/reoxygenation-exposed primary human trophoblasts (PHTs) and the preeclampsia placenta using complementary approaches, including a novel protein aggregate detection assay. Mechanistic analysis was performed in hypoxia/reoxygenation-exposed PHTs and

resultsTTR aggregation was inducible in PHTs and the TCL-1 trophoblast cell line by endoplasmic reticulum stress inducers or autophagy-lysosomal disruptors. PHTs exposed to hypoxia/reoxygenation showed increased intracellular BiP (binding immunoglobulin protein), phosphorylated IRE1α (inositol-requiring enzyme-1α), PDI (protein disulfide isomerase), and Ero-1, all markers of the unfolded protein response, and the apoptosis mediator caspase-3. Blockade of IRE1α inhibited hypoxia/reoxygenation-induced upregulation of Ero-1 in PHTs. Excessive unfolded protein response activation was observed in the early-onset preeclampsia placenta. Importantly, pregnant human TTR mice displayed aggregated TTR in the junctional zone of the placenta and severe preeclampsia-like features. High-resolution ultrasound analysis revealed low blood flow in uterine and umbilical arteries in human TTR mice compared with control mice. However,

conclusionsThese observations in the preeclampsia placenta, cultured trophoblasts, and

Indexed as

Pre-EclampsiaTrophoblastsAnimalsCarrier ProteinsEndoplasmic ReticulumEndoplasmic Reticulum StressEndoribonucleasesFemaleHumansHypoxiaMiceMice, TransgenicPlacentaPrealbuminPregnancyProtein AggregatesCarrier ProteinsEndoribonucleasesPrealbuminProtein AggregatesProtein Serine-Threonine Kinasesautophagyendoplasmic reticulum stresslysosomesplacentaunfolded protein response

Identifiers

PMID35607996
PMCPMC9308752
OpenAlexW4282941451

What OpenQuestion holds

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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.