Evidence map›Paper›PMID 39601641›Full record

ArticleImmunity, inflammation and disease2024

Salirasib Inhibits the Expression of Genes Involved in Fibrosis in Fibroblasts of Systemic Sclerosis Patients.

Mina Sadeghi Shaker, Mohsen Rokni, Hoda Kavosi, Samaneh Enayati, Elham Madreseh, Mahdi Mahmoudi, Elham Farhadi, Mohammad Vodjgani

Abstract read
In one paragraph

Article in Immunity, inflammation and disease, 2024. 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

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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

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Mina Sadeghi ShakerDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mohsen RokniDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Hoda KavosiRheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.ORCID 0000-0003-4762-6943
Samaneh EnayatiRheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Elham MadresehRheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Mahdi MahmoudiRheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.ORCID 0000-0002-8164-8831
Elham FarhadiRheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.ORCID 0000-0002-4324-2697
Mohammad VodjganiDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Funding

This study was supported by the Tehran University of Medical Sciences and Health Services (Grant Number 99-3-130-50940).
6 · The paper itself

Abstract

backgroundFibrosis is a principal sign of systemic sclerosis (SSc) which can affect several organs including the lung, heart, and dermis. Dermal fibroblasts of SSc patients are characterized by persistent and activated Ras and ERK1/2 signaling which stimulates extreme collagen and extracellular matrix synthesis. Salirasib is a Ras inhibitor that competitively prevents the adherence of GTP-bound Ras to the plasma membrane, that inhibits Ras signaling. This study intended to clarify whether salirasib can influence fibrotic mediators in SSc fibroblasts. MATERIALS AND

methodsDermal fibroblasts from 10 SSc patients were treated with salirasib in the presence of TGF-β1, and mRNA levels of H-Ras and genes related to fibrosis, such as COL1A1, COL1A2, CTGF, TGF-β1, fibronectin, ACTA2, and MMP1 was measured by real-time PCR. The α-SMA protein expression was analyzed by immunofluorescence staining.

resultsIn dermal fibroblasts of SSc patients, salirasib treatment, markedly downregulated the H-Ras gene expression. In addition, the protein expression of α-SMA and gene expression of ACTA2 were inhibited upon salirasib treatment. Salirasib also significantly reduced the expression of COL1A1, and COL1A2 genes and augmented the gene expression of MMP1. The mRNA levels of other genes related to fibrosis such as FN1, CTGF, and TGF-β1 were significantly decreased upon salirasib treatment.

conclusionConsidering salirasib significantly reduced the expression of genes related to the fibrosis process and α-SMA gene and protein expression, and given significant upregulation of MMP1 by salirasib, it can be considered as a new curative strategy for fibrotic diseases like SSc.

Indexed as

Connective Tissue Growth FactorFibroblastsFibrosisScleroderma, SystemicActinsAdultCells, CulturedCollagen Type ICollagen Type I, alpha 1 ChainFemaleFibronectinsGene Expression RegulationHumansMaleMatrix Metalloproteinase 1Middle AgedACTA2 protein, humanActinsCCN2 protein, humanCollagen Type ICollagen Type I, alpha 1 ChainConnective Tissue Growth FactorFibronectinsMatrix Metalloproteinase 1MMP1 protein, humanras ProteinsTransforming Growth Factor beta1dermal fibroblastfibrosissalirasibsystemic sclerosisTGF‐β1

Identifiers

PMID39601641
PMCPMC11600624

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