Evidence map›Paper›PMID 38305495›Full record

ArticleRheumatology (Oxford, England)2024

Long non-coding RNA H19X as a regulator of mononuclear cell adhesion to the endothelium in systemic sclerosis.

Francesca Tirelli, Elena Pachera, Sabrina Gmür, Robert Lafyatis, Mengqi Huang, Francesco Zulian, Eva Camarillo Retamosa, Gabriela Kania, Oliver Distler

Open access · greenAbstract read
In one paragraph

Article in Rheumatology (Oxford, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact, top 98% 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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

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

9 authors at 3 institutions in 3 countries.

Francesca TirelliCenter of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-9947-4059
Elena PacheraCenter of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-5157-3808
Sabrina GmürCenter of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Robert LafyatisDivision of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Mengqi HuangDivision of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Francesco ZulianRheumatology Unit, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy.ORCID 0000-0002-2479-3485
Eva Camarillo RetamosaCenter of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Gabriela KaniaCenter of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Oliver DistlerCenter of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-0546-8310
University of Zurich · CHUniversity of Padua · ITUniversity of Pittsburgh · US

Funding

Translational studies for identifying and targeting novel pathways in systemic sclerosis pathogenesisP50AR060780 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LAFYATIS, ROBERT A. · 2011 to 2021
$14.9M
Open chromatin and transcriptional regulation of dermal myofibroblasts in SScR61AR076819 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LAFYATIS, ROBERT A. · 2019 to 2019
$388k
National Scleroderma FoundationNIAMS NIH HHS P50 AR060780NIAMS NIH HHS P50AR060780-07NIAMS NIH HHS R61 AR076819
6 · The paper itself

Abstract

objectiveTo define the functional relevance of H19 X-linked (H19X) co-expressed long non-coding RNA (lncRNA) in endothelial cell (EC) activation as a key process in SSc vasculopathy.

methodsH19X expression in SSc skin biopsies was analysed from single-cell RNA sequencing (scRNA-seq) data. Differential expression and pathway enrichment analysis between cells expressing (H19Xpos) and non-expressing H19X (H19Xneg) cells was performed. H19X function was investigated in human dermal microvascular ECs (HDMECs) by silencing. H19X and EC adhesion molecule levels were analysed by real-time quantitative PCR and western blot after stimulation with pro-inflammatory cytokines. Cytoskeletal rearrangements were analysed by fluorescent staining. Endothelial adhesion was evaluated by co-culture of HDMECs and fluorescent-labelled peripheral blood mononuclear cells (PBMCs). Shedding vascular cell adhesion protein 1 (VCAM1) was evaluated by ELISA on HDMEC supernatant.

resultsThe scRNA-seq data showed significant upregulation of H19X in SSc compared with healthy ECs. In HDMECs, H19X was consistently induced by IFN type I and II. H19X knockdown lead to a significant decrease in the mRNA of several adhesion molecules. In particular, VCAM1 was significantly reduced at the protein and mRNA levels. Co-expression analysis of the scRNA-seq data confirmed higher expression of VCAM1 in H19Xpos ECs. ECs were also strongly associated with the 'cell adhesion molecule' pathway. Moreover, the VCAM1 downstream pathway displayed less activation following H19X knockdown. Contractility of HDMECs, PBMC adhesion to HDMECs and VCAM1 shedding were also reduced following H19X knockdown.

conclusionslncRNA H19X may contribute to EC activation in SSc vasculopathy, acting as a regulator of expression of adhesion molecules in ECs.

Indexed as

Cell AdhesionEndothelial CellsLeukocytes, MononuclearRNA, Long NoncodingScleroderma, SystemicVascular Cell Adhesion Molecule-1Cells, CulturedEndothelium, VascularHumansSkinUp-RegulationH19 long non-coding RNARNA, Long NoncodingVascular Cell Adhesion Molecule-1activated endotheliumadhesion moleculesH19Xinterferonslong non-coding RNAmicrovascular endothelial cellsscRNA-seqsystemic sclerosisvasculopathyVCAM1

Identifiers

PMID38305495
PMCPMC11443020
OpenAlexW4391463652

What OpenQuestion holds

Textmetadata
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.