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Endoglin differentially modulates antagonistic transforming growth factor-beta1 and BMP-7 signaling

Olaf Scherner1, Steffen K Meurer, Lidia Tihaa

  • 1Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital, Aachen, Germany.

The Journal of Biological Chemistry
|March 23, 2007
PubMed

Insights

Transforming growth factor-beta1 and bone morphogenetic protein-7 have opposing roles in kidney fibrosis. Endoglin influences these pathways, enhancing BMP-7 signaling while inhibiting TGF-beta1 signaling.

Area of Science:

  • Cell biology
  • Molecular signaling
  • Renal pathophysiology

Background:

  • Transforming growth factor-beta1 (TGF-beta1) and bone morphogenetic protein-7 (BMP-7) are key antagonistic cytokines in kidney fibrosis.
  • Endoglin (CD105), a TGF-beta type III receptor, is upregulated in kidney fibrosis and known to negatively regulate TGF-beta signaling.
  • The interplay between TGF-beta1, BMP-7, and endoglin in cellular signaling requires further elucidation.

Purpose of the Study:

  • To investigate the effect of BMP-7 on TGF-beta1 signaling pathways.
  • To determine the role of endoglin in mediating BMP-7 and TGF-beta1 signaling.
  • To analyze the impact of these interactions on myogenic differentiation and target gene expression.

Main Methods:

  • Utilized endoglin-deficient L(6)E(9) myoblastic cells.
  • Analyzed TGF-beta1 and BMP-7 induced gene expression (e.g., collagen I, Id1).
  • Investigated activation of specific signaling pathways, including ALK-5/Smad3 and ALK-1/Smad1/Smad5.

Main Results:

  • TGF-beta1 activated both ALK-5/Smad3 (collagen I) and ALK-1/Smad1/Smad5 (transient Id1) pathways.
  • BMP-7 exclusively activated Smad1/Smad5 (prolonged Id1) and antagonized TGF-beta1-induced collagen I expression via ALK-5/Smad3.
  • Endoglin overexpression enhanced BMP-7/Smad1/Smad5 signaling while inhibiting TGF-beta1/ALK-5/Smad3 signaling.

Conclusions:

  • BMP-7 antagonizes TGF-beta1-induced collagen I expression through the ALK-5/Smad3 pathway.
  • Endoglin plays a differential role, enhancing BMP-7 signaling and inhibiting TGF-beta1 signaling.
  • These findings provide insights into the complex regulation of kidney fibrosis by TGF-beta1, BMP-7, and endoglin.

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