Evidence map›Paper›PMID 40885718›Full record

ArticleCell death & disease2025

Long noncoding RNA H19 promotes the acquisition of a mesenchymal-like invasive phenotype in mesothelial primary cells through an HDAC1-mediated WT1/Sp1 switch.

Giulio Bontempi, Federica Michetti, Michela Terri, Cecilia Battistelli, Alice Conigliaro, Sabrina Garbo, Claudia Montaldo, Sergio Valente, Clemens Zwergel, Antonello Mai and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

15 authors.

Giulio BontempiDepartment of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Federica MichettiDepartment of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Michela TerriDepartment of Molecular Medicine, Sapienza University of Rome, Rome, Italy.ORCID http://orcid.org/0000-0003-1090-7012
Cecilia BattistelliDepartment of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Alice ConigliaroDepartment of Biomedicine, Neurosciences and Advanced Diagnostics (Bi.N.D.), Section of Biology and Genetics, University of Palermo, Palermo, Italy.ORCID http://orcid.org/0000-0002-3037-835X
Sabrina GarboDepartment of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Claudia MontaldoGene Expression Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy.
Sergio ValenteDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.ORCID http://orcid.org/0000-0002-2241-607X
Clemens ZwergelDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.ORCID http://orcid.org/0000-0002-3097-0003
Antonello MaiDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.ORCID http://orcid.org/0000-0001-9176-2382
Azadeh Nahavandi AraghiEscuela de Doctorado,, Universidad Autónoma de Madrid, Madrid, Spain.
Alessandro DomeniciRenal Unit, Department of Clinical and Molecular Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy.
Paolo MenèRenal Unit, Department of Clinical and Molecular Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy.
Marco TripodiDepartment of Molecular Medicine, Sapienza University of Rome, Rome, Italy.ORCID http://orcid.org/0000-0001-6135-971X
Raffaele StrippoliDepartment of Molecular Medicine, Sapienza University of Rome, Rome, Italy. raffaele.strippoli@uniroma1.it.ORCID http://orcid.org/0000-0003-3483-8381

Funding

Ministero della Salute (Ministry of Health, Italy) Ricerca corrente linea 3 I.N.M.I. L. Spallanzani IRCCS
6 · The paper itself

Abstract

Peritoneal fibrosis is a pathological alteration of the peritoneal membrane occurring in pro-inflammatory conditions, including peritoneal dialysis (PD), a renal replacement therapy. Characteristic of this process is the acquisition of invasive/pro-fibrotic abilities by mesothelial cells (MCs) through induction of mesothelial to mesenchymal transition (MMT), a cell-specific form of EMT. Long noncoding (lnc) RNAs act as major players in physiologic regulatory circuitries of the cell. While LncRNA-H19 (lncH19), one of the first lncRNAs identified, has been broadly studied in tumorigenesis, its role in peritoneum fibrotic diseases has been scarcely addressed so far. Aim of this study was to investigate the role of H19 in the acquisition of a mesenchymal-like phenotype in primary fibrotic MCs from PD patients, and to elucidate epigenetic mechanisms controlling its expression. Genetic silencing/ectopic expression experiments revealed that H19 promoted the expression of MMT markers while downregulating the epithelial marker E-Cadherin, and favored MC directed migration and invasion on a collagen matrix. Silencing of three main H19 isoforms revealed a synergistic activity in the induction of a mesenchymal phenotype. Treatment with MS-275, an HDAC1-3 specific inhibitor previously known to promote MMT reversal, as well as HDAC1 genetic silencing, downregulated lncRNA H19 expression. Bioinformatic analysis revealed a binding sequence of Wilm's Tumor Protein 1 (WT1), the master gene of mesothelial differentiation, on the H19 promoter at an area with multiple acetylation peaks partially overlapping the binding site of Specificity protein 1 (Sp1), another transcription factor active in cellular plasticity regulation. Genetic silencing and Chromatin Immunoprecipitation (ChIP) experiments demonstrated that HDAC1 inhibition promotes a switch between WT1 and Sp1 in H19 promoter occupancy, favoring an inhibitory effect of WT1 on H19 expression and the reversal towards an epithelial-like phenotype. Overall, we discovered an HDAC1-WT1/Sp1-H19 axis potentially relevant to the design of new therapies aimed at counteracting peritoneal fibrosis.

Indexed as

Histone Deacetylase 1RNA, Long NoncodingSp1 Transcription FactorWT1 ProteinsCell MovementEpithelial CellsEpithelial-Mesenchymal TransitionEpitheliumHumansPhenotypePromoter Regions, GeneticH19 long non-coding RNAHDAC1 protein, humanHistone Deacetylase 1RNA, Long NoncodingSP1 protein, humanSp1 Transcription FactorWT1 protein, humanWT1 Proteins

Identifiers

PMID40885718
PMCPMC12398590

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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.