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Updated: Jan 12, 2026

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The Function of the TGFβ Signaling Pathway in Connective Tissue Diseases: From Biology to Clinical Application

Simin Yuan1, Wen Zhu2, Yue Wang1,2

  • 1Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, People's Republic of China.

Journal of Inflammation Research
|October 30, 2025
PubMed

Insights

Transforming growth factor-β (TGFβ) signaling drives fibrosis and immune dysfunction in connective tissue diseases (CTDs). Targeting TGFβ offers potential therapeutic strategies for CTDs, addressing fibrosis and immune abnormalities.

Area of Science:

  • Immunology
  • Cell Biology
  • Rheumatology

Background:

  • Connective tissue diseases (CTDs) involve inflammation, immune dysfunction, and fibrosis.
  • Transforming growth factor-β (TGFβ) signaling is implicated in CTD pathogenesis, including fibroblast activation and extracellular matrix accumulation.

Purpose of the Study:

  • To review the dual role of TGFβ signaling in CTD pathogenesis.
  • To explore TGFβ's mechanistic role in specific CTDs like SSc, SLE, RA, and SS.
  • To discuss therapeutic challenges and opportunities targeting TGFβ in CTDs.

Main Methods:

  • Systematic literature search of PubMed and Web of Science.
  • Narrative review of existing research on TGFβ signaling in CTDs.
  • Analysis of classical and non-classical TGFβ pathways in fibrosis and immunomodulation.

Main Results:

  • TGFβ signaling critically influences fibroblast activation, ECM accumulation, and immune cell activity in CTDs.
  • The pathway plays a complex role in the pathogenesis of systemic sclerosis, lupus, rheumatoid arthritis, and Sjögren's syndrome.
  • Interplay between TGFβ pathways impacts fibrosis and immune regulation.

Conclusions:

  • TGFβ signaling is a pivotal factor in CTD-associated fibrosis and immune dysregulation.
  • Targeting TGFβ presents therapeutic potential for managing CTD symptoms.
  • Further research can lead to precise, individualized treatment strategies for connective tissue diseases.
Keywords:
TGF-β signaling pathwayconnective tissue disordersfibrosisimmunomodulationtherapeutic targets

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