Evidence map›Paper›PMID 40234537›Full record

ArticleScientific reports2025

Cystatin 6 (CST6) and Legumain (LGMN) are potential mediators in the pathogenesis of preeclampsia.

Stefan M Botha, Lucy A Bartho, Sunhild Hartmann, Ping Cannon, Anna Nguyen, Tuong-Vi Nguyen, Natasha Pritchard, Ralf Dechend, Olivia Nonn, Stephen Tong and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Application of single-cell RNA sequencing in preeclampsia.Frontiers in global women's health · 2026
    Review
  3. Article
  4. Review
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.

Stefan M BothaTranslational Obstetrics Group, The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, 3084, Australia. bothas@student.unimelb.edu.au.
Lucy A BarthoTranslational Obstetrics Group, The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, 3084, Australia.
Sunhild HartmannTranslational Obstetrics Group, The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, 3084, Australia.
Ping CannonTranslational Obstetrics Group, The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, 3084, Australia.
Anna NguyenTranslational Obstetrics Group, The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, 3084, Australia.
Tuong-Vi NguyenTranslational Obstetrics Group, The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, 3084, Australia.
Natasha PritchardMercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
Ralf DechendCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Olivia NonnCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Stephen TongTranslational Obstetrics Group, The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, 3084, Australia.
Tu'uhevaha J Kaitu'u-LinoTranslational Obstetrics Group, The Department of Obstetrics, Gynaecology and Newborn Health, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, 3084, Australia.

Funding

National Health and Medical Research Council 1065854
6 · The paper itself

Abstract

Preeclampsia results from placental insufficiency and causes maternal endothelial dysfunction and multi-organ damage. Our in-silico analysis identified Cystatin 6 (CST6), a cysteine protease inhibitor, as located on the placental surface where it might be released into maternal circulation. This study aimed to characterise CST6 and one of its high affinity targets, Legumain (LGMN), in preeclampsia and assess its biomarker potential by measuring levels in maternal circulation. Placental CST6 mRNA expression was significantly increased in 78 pregnancies complicated by early-onset preeclampsia (delivering at < 34 weeks' gestation) relative to 30 gestation matched controls (P < 0.0001). LGMN mRNA expression was significantly decreased (P = 0.0309). Circulating CST6 was increased in 35 pregnancies complicated by early-onset preeclampsia (< 34 weeks' gestation) relative to 27 gestation matched controls (P = 0.0261), and LGMN levels remained unchanged. At 36 weeks' gestation, circulating CST6 was significantly increased (P = 0.001), while LGMN was significantly decreased (P = 0.0135) in 21 pregnancies preceding diagnosis of preeclampsia at term, compared to 184 pregnancies that did not develop preeclampsia. Human trophoblast stem cells (hTSC) were differentiated into syncytiotrophoblast or extravillous trophoblast (EVT) to evaluate CST6 and LGMN expression in these trophoblast lineages. CST6 and LGMN mRNA expression were significantly increased across 96 h after syncytiotrophoblast (P = 0.0066 and P = 0.0010 respectively) and EVT differentiation (P = 0.0618 and P = 0.0016 respectively), with the highest expression in syncytiotrophoblast. Computational analysis of two publicly available single-cell and single-nuclei RNA sequencing datasets correlated with the expression pattern observed in vitro. When syncytiotrophoblast cells were exposed to hypoxia (1% O

Indexed as

CystatinsCysteine EndopeptidasesPre-EclampsiaAdultAsparaginyl EndopeptidaseBiomarkersCase-Control StudiesFemaleHumansPlacentaPregnancyRNA, MessengerTrophoblastsAsparaginyl EndopeptidaseBiomarkersCystatinsCysteine EndopeptidasesRNA, MessengerCST6Cystatin 6LegumainLGMNPlacentaPreeclampsiaPregnancyTrophoblast

Identifiers

PMID40234537
PMCPMC12000359

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.