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Updated: Jun 22, 2026

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
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Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

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Signaling in fibrosis: targeting the TGF beta, endothelin-1 and CCN2 axis in scleroderma

Andrew Leask1

  • 1CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology, Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London ON, Canada. Andrew.Leask@schulich.uwo.ca

Frontiers in Bioscience (Elite Edition)
|June 2, 2009
PubMed

Insights

Fibrosis, a fibrotic disease affecting multiple organs, lacks effective therapies. Recent research highlights transforming growth factor beta (TGF-β) signaling as a key driver, involving proteins like endothelin-1 (ET-1) and CCN2 (CTGF).

Area of Science:

  • Fibrosis research
  • Molecular signaling pathways
  • Connective tissue disorders

Background:

  • Fibrosis significantly impacts organs like skin, liver, kidney, and lung, leading to high morbidity.
  • Currently, no specific therapies exist to treat or reverse fibrosis.
  • Transforming growth factor beta (TGF-β) signaling is a critical pathway implicated in fibrogenesis.

Purpose of the Study:

  • To review recent molecular insights into fibrosis signaling.
  • To emphasize the role of TGF-β signaling in fibrotic diseases.
  • To focus on the contribution of endothelin-1 (ET-1) and CCN2 (CTGF) in fibrosis, particularly in scleroderma.

Main Methods:

  • Literature review of recent molecular studies on fibrosis.
  • Analysis of signaling mechanisms involving TGF-β.
  • Investigation of the roles of ET-1 and CCN2 in fibrotic processes.

Main Results:

  • Transforming growth factor beta (TGF-β) signaling is a major driver of fibrogenesis.
  • The precise signaling pathways of TGF-β in inducing fibrotic responses are under intense investigation.
  • Endothelin-1 (ET-1) and CCN2 (connective tissue growth factor, CTGF) are identified as crucial pro-fibrotic proteins, potentially acting as downstream regulators or co-factors of TGF-β signaling.

Conclusions:

  • Understanding TGF-β signaling and its associated proteins (ET-1, CCN2) is crucial for developing anti-fibrotic therapies.
  • Recent molecular discoveries offer new avenues for targeting fibrosis.
  • Further research into these pathways is essential, especially for diseases like scleroderma.

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