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ArticleClinical rheumatology2026

Upregulation of RAF and RalGDS gene expression by TGF-β in systemic sclerosis dermal fibroblasts: a controlled in vitro study.

Fatemeh Bakhshi, Mehrdad Mahalleh, Hoda Kavosi, Zahra Jafarisavari, Nooshin Ahmadzadeh, Samaneh Enayati, Elham Madreseh, Behrouz Robat-Jazi, Mahdi Mahmoudi, Elham Farhadi and 1 more

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Article in Clinical rheumatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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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

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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

1 citing paper in PubMed.

  1. Review
4 · The record

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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.

Fatemeh Bakhshi *Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mehrdad Mahalleh *Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Hoda KavosiRheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Zahra JafarisavariRheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Nooshin AhmadzadehRheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Samaneh EnayatiRheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Elham MadresehRheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Behrouz Robat-JaziRheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Mahdi MahmoudiResearch Center for Chronic Inflammatory Diseases, Tehran University of Medical Sciences, Tehran, Iran.
Elham FarhadiRheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. farhadie@tums.ac.ir.ORCID http://orcid.org/0000-0002-4324-2697
Mohammad VodjganiDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. vojganim@tums.ac.ir.

Funding

Tehran University of Medical Sciences 1402-1-101-65423
6 · The paper itself

Abstract

introductionSystemic sclerosis is an autoimmune rheumatic disorder characterized by uncontrolled fibroblast activation, skin thickening, and fibrosis. Activated Ras and ERK signaling significantly affect fibrosis and EMT upon TGF-β treatment. RalGDS may play an important role in inflammatory and oncogenic processes. This study investigates the expression of RAF and RalGDS genes in SSc patients compared to healthy individuals before and after treatment with TGF-β.

methodsThis research included 20 patients with systemic sclerosis and 18 healthy controls matched for age and sex. Skin biopsies were collected, and fibroblasts were grown and expanded. The identity of fibroblasts was confirmed using immunofluorescence labeling. Fibroblasts were subjected to TGF-β1 treatment, and the expression levels of A-RAF, B-RAF, C-RAF, and RalGDS genes were assessed via real-time PCR.

resultsGene expression analysis revealed no significant baseline changes in RAF and RalGDS between groups; however, TGF-β therapy dramatically raised both genes in SSc cells relative to controls. A positive association was identified between the expression levels of the RAF and RalGDS genes.

conclusionsThis study investigated A-RAF, B-RAF, C-RAF, and RalGDS gene expression in fibroblasts from SSc patients and healthy controls, focusing on their response to TGF-β treatment. While baseline expression levels were similar between groups, TGF-β significantly upregulated these genes in SSc fibroblasts more than in controls. This suggests that TGF-β signaling may contribute to the dysregulation of RAF and RalGDS pathways in SSc, highlighting their potential as biomarkers and therapeutic targets for the disease. Key Points • No significant difference in gene expression levels between SSc and healthy fibroblasts. • SSc and healthy fibroblasts exhibit upregulated RAF and RalGDS expression at the mRNA level in response to TGF-β treatment. • Positive correlation between the expression levels of A-RAF and B-RAF, B-RAF and C-RAF, and finally between C-RAF and RalGDS genes.

Indexed as

FibroblastsScleroderma, SystemicTransforming Growth Factor betaAdultAgedCase-Control StudiesCells, CulturedFemaleHumansMaleMiddle AgedSkinUp-RegulationTransforming Growth Factor betaFibroblastsFibrosisRAFRalGDSRASSystemic sclerosisTransforming growth factor beta

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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.