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Related Experiment Video

Updated: Jan 12, 2026

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Systemic sclerosis, main culprits and involved signaling pathways.

Omid Sadatpour1,2, Amin Azizan2,3, Hoda Kavosi2,3

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

Inflammation Research : Official Journal of the European Histamine Research Society ... [Et Al.]
|November 6, 2025
PubMed
Summary

Systemic sclerosis involves autoimmune fibrosis driven by cytokines like TGF-β. Key cells and signaling pathways, including macrophage polarization, contribute to this complex connective tissue disease.

Keywords:
FibrosisSignaling pathwaysSystemic sclerosisTGF-β

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Area of Science:

  • Immunology
  • Cell Biology
  • Rheumatology

Background:

  • Systemic sclerosis is an autoimmune connective tissue disease with varied manifestations.
  • Raynaud's phenomenon, triggered by cold or stress, often signals disease onset.
  • Unknown etiology contributes to the complexity of systemic sclerosis.

Purpose of the Study:

  • To elucidate the cellular and molecular mechanisms driving fibrosis in systemic sclerosis.
  • To understand the role of cytokines and signaling pathways in disease pathogenesis.
  • To investigate the contribution of different cell types to extracellular matrix accumulation.

Main Methods:

  • Analysis of cytokine signaling, particularly TGF-β.
  • Examination of cellular responses in vascular endothelial cells, smooth muscle cells, and fibroblasts.
  • Investigation of macrophage polarization (M1/M2) in the disease microenvironment.
  • Assessment of signaling pathways like AKT, MAPK, GPCR, and Ras.

Main Results:

  • TGF-β drives fibrosis in inflammatory and hypoxic conditions.
  • Activated monocytes differentiate into M1 macrophages early and M2 macrophages during fibrosis.
  • Fibroblast activation via TGF-β leads to extracellular matrix accumulation.
  • Signaling pathways (AKT, MAPK, GPCR, Ras) promote disease progression.

Conclusions:

  • Multiple cell types and signaling pathways contribute to systemic sclerosis pathogenesis.
  • Cytokines and macrophage polarization are critical in the inflammatory and fibrotic phases.
  • Understanding these mechanisms is key to developing targeted therapies for systemic sclerosis.