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

Fatemeh Bakhshi1,2, Mehrdad Mahalleh2, Hoda Kavosi2,3

  • 1Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Clinical Rheumatology
|November 5, 2025
PubMed
Abstract

Insights

Systemic sclerosis (SSc) fibroblasts show increased RAF and RalGDS gene expression after TGF-β treatment compared to healthy controls, suggesting potential therapeutic targets for SSc.

Area of Science:

  • Rheumatology
  • Molecular Biology
  • Cell Biology

Background:

  • Systemic sclerosis (SSc) is an autoimmune disease marked by fibroblast activation and fibrosis.
  • Ras and ERK signaling pathways are implicated in SSc fibrosis and epithelial-to-mesenchymal transition (EMT).
  • RalGDS is potentially involved in inflammatory and oncogenic processes relevant to SSc.

Purpose of the Study:

  • To investigate the expression of RAF (A-RAF, B-RAF, C-RAF) and RalGDS genes in systemic sclerosis (SSc) patients.
  • To compare gene expression in SSc patients versus healthy controls before and after TGF-β treatment.
  • To explore the role of TGF-β in regulating RAF and RalGDS expression in SSc.

Main Methods:

  • Recruited 20 SSc patients and 18 healthy controls.
  • Collected skin biopsies and cultured fibroblasts, confirming identity via immunofluorescence.
  • Treated fibroblasts with TGF-β1 and assessed A-RAF, B-RAF, C-RAF, and RalGDS gene expression using real-time PCR.

Main Results:

  • No significant baseline differences in RAF and RalGDS gene expression between SSc and control fibroblasts.
  • TGF-β treatment significantly upregulated RAF and RalGDS gene expression in SSc fibroblasts compared to controls.
  • A positive correlation was observed between the expression levels of RAF isoforms and RalGDS.

Conclusions:

  • TGF-β signaling contributes to the dysregulation of RAF and RalGDS pathways in SSc.
  • Upregulated RAF and RalGDS expression in SSc fibroblasts post-TGF-β treatment suggests their potential as SSc biomarkers.
  • These genes represent potential therapeutic targets for managing SSc fibrosis and related complications.
Keywords:
FibroblastsFibrosisRAFRASRalGDSSystemic sclerosisTransforming growth factor beta

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