Evidence map›Paper›PMID 40638678›Full record

ArticlePloS one2025

Altered Bcl-2/Caspase signaling and hypoxia-induced apoptosis in primary human aniridia limbal stromal cells, in CoCl2 mediated hypoxic stress, in vitro.

Shanhe Liu, Shuailin Li, Shao-Lun Hsu, Fabian N Fries, Zhen Li, Swarnali Kundu, Berthold Seitz, Maryam Amini, Shweta Suiwal, Julia Zimmermann and 3 more

Abstract read
In one paragraph

Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
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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

13 authors.

Shanhe LiuDr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Homburg/Saar, Germany.ORCID https://orcid.org/0000-0001-8096-4771
Shuailin LiDr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Homburg/Saar, Germany.ORCID https://orcid.org/0009-0007-2251-6242
Shao-Lun HsuDr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Homburg/Saar, Germany.ORCID https://orcid.org/0000-0001-5235-5039
Fabian N FriesDr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Homburg/Saar, Germany.ORCID https://orcid.org/0000-0002-8526-4712
Zhen LiDr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Homburg/Saar, Germany.
Swarnali KunduDr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Homburg/Saar, Germany.
Berthold SeitzDepartment of Ophthalmology, Saarland University Medical Center, Homburg/Saar, Germany.ORCID https://orcid.org/0000-0001-9701-8204
Maryam AminiDr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Homburg/Saar, Germany.
Shweta SuiwalDr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Homburg/Saar, Germany.
Julia ZimmermannDr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Homburg/Saar, Germany.
Simon TrusenDr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Homburg/Saar, Germany.
Tanja StachonDr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Homburg/Saar, Germany.
Nóra SzentmáryDr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Homburg/Saar, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe aim of this study was to investigate apoptosis in primary aniridia limbal stromal cells (LSCs) and to assess changes in the expression of genes and proteins associated with the apoptotic pathway in response to cobalt chloride (CoCl2)-induced hypoxic stress, in vitro.

methodsPrimary human limbal stromal cells were isolated from the limbal region of both aniridia (AN-LSCs; n = 8) and healthy (LSCs; n = 8) donors. The cells were treated with 0 µM, 50 µM, and 75 µM CoCl2 for 48 hours. Apoptosis in each group was assessed by Flow cytometry (FC). The expression levels of apoptosis-related genes, including CASP 3/7/8/9/10, BCL2, BID, BAX, CDKN1A (p21), CDKN1B (p27), TNFα, XIAP, and BIRC5 (Survivin), were measured by qPCR. Protein level of these markers was analyzed by FC. TNFα protein expression in the supernatant was quantified using ELISA.

resultsFlow cytometry analysis revealed a significantly higher apoptosis rate in AN-LSCs compared to LSCs (p < 0.0001). In AN-LSCs, treatment with 75 µM CoCl₂ further increased the apoptosis rate compared to untreated AN-LSCs (p = 0.047). BCL2 mRNA levels (p = 0.0291), Caspase-8 (p = 0.0341), Caspase-10 (p = 0.0085), Bcl-2 (p = 0.0014), XIAP (p = 0.0003) and Survivin (p = 0.0074) protein levels were significantly higher in LSCs than in AN-LSCs. Conversely, Caspase-3 (p = 0.0366), Caspase-9 (p = 0.0354), p21 (p = 0.0003), and p27 (p = 0.0164) protein levels were significantly higher in AN-LSCs than in LSCs. In LSCs, exposure to 75 µM CoCl₂ led to a reduction in BCL2 mRNA (p = 0.0102) and protein levels (p = 0.0484), accompanied by an increase in CDKN1B mRNA level (p = 0.0265). In AN-LSCs, 75 µM CoCl₂ treatment resulted in a decrease in CASP3 (p = 0.049), CASP7 (p = 0.041) and BCL2 (p = 0.0218) mRNA and Bcl-2 protein levels (p = 0.0405) and an increase of TNF-α protein levels in the cell culture supernatant (p = 0.0251).

conclusionsThe apoptosis rate of LSCs from patients with congenital aniridia is higher than that of the control group, accompanied by alterations in multiple apoptosis-related markers. Additionally, CoCl₂-induced hypoxic stress further increases apoptosis in AN-LSCs and leads to changes in the expression of Caspase 3, Caspase 7, Bcl-2, and CDKN1B (p27). Further research is needed to elucidate the potential therapeutic targets in AAK, with the aim of preventing or slowing the progression of aniridia-associated keratopathy.

Indexed as

ApoptosisCaspasesCobaltLimbus CorneaeProto-Oncogene Proteins c-bcl-2Signal TransductionStromal CellsAdultCell HypoxiaCells, CulturedFemaleHumansMaleTumor Necrosis Factor-alphaBCL2 protein, humanCaspasesCobaltcobaltous chlorideProto-Oncogene Proteins c-bcl-2Tumor Necrosis Factor-alpha

Identifiers

PMID40638678
PMCPMC12244546

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