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Updated: May 29, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

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Published on: August 3, 2018

Connective tissue growth factor antagonizes transforming growth factor-β1/Smad signalling in renal mesangial cells

Helen C O'Donovan1, Fionnuala Hickey, Derek P Brazil

  • 1University College Dublin School of Biomolecular and Biomedical Science, Belfield, Dublin 4, Republic of Ireland.

The Biochemical Journal
|August 30, 2011
PubMed

Insights

Connective tissue growth factor (CTGF) regulates transforming growth factor-β1 (TGF-β1) signaling in diabetic nephropathy (DN). CTGF binding to TGF-β type III receptor antagonizes canonical TGF-β1 pathways, offering a potential therapeutic target for DN.

Area of Science:

  • Nephrology
  • Cell Biology
  • Molecular Biology

Background:

  • Transforming growth factor-β1 (TGF-β1) critically mediates diabetic nephropathy (DN).
  • The regulatory role of connective tissue growth factor (CTGF) in TGF-β1 signaling networks within DN remains unclear.

Purpose of the Study:

  • To investigate the cooperative signaling between CTGF and TGF-β1.
  • To elucidate the physiological significance of CTGF-TGF-β1 interactions in DN.

Main Methods:

  • Investigated CTGF binding to TGF-β type III receptor (TβRIII).
  • Assessed Smad phosphorylation and gene expression in mesangial cells treated with CTGF/TGF-β1.
  • Analyzed STZ-induced diabetic mouse models and human renal biopsy samples.

Main Results:

  • CTGF directly binds TβRIII, antagonizing TGF-β1-induced Smad signaling and gene expression.
  • CTGF inhibits TGF-β1 binding to its receptor, promoting non-canonical TGF-β1 signaling.
  • STZ-induced diabetic mice showed decreased Smad phosphorylation and increased CTGF; TβRIII knockdown restored TGF-β1 signaling.
  • Gene expression profiles correlated between treated cells and human DN samples.

Conclusions:

  • Mesangial cell responses to TGF-β1 are modulated by cross-talk with CTGF.
  • TβRIII is crucial for CTGF-mediated regulation of TGF-β1 signaling.
  • Targeting CTGF presents a potential therapeutic strategy for diabetic nephropathy.

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