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Editorial
. 2008 Aug;58(8):2219-24.
doi: 10.1002/art.23634.

Molecular ablation of transforming growth factor beta signaling pathways by tyrosine kinase inhibition: the coming of a promising new era in the treatment of tissue fibrosis

Joel Rosenbloom  1 , Sergio A Jiménez
Affiliations
Editorial

Molecular ablation of transforming growth factor beta signaling pathways by tyrosine kinase inhibition: the coming of a promising new era in the treatment of tissue fibrosis

Joel Rosenbloom et al. Arthritis Rheum. 2008 Aug.
No abstract available

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Figures

Figure 1
Figure 1. TGF-β signaling pathways critical for the fibrotic response
Illustrated are two canonical Smad pathways originating from two representative tetrameric receptors. After TGF-β binding, the TGFβRII receptor recruits a type1 receptor (TGFβRI) and activates it by phosphorylation. Alk-5 then specifically phosphorylates receptor-regulated Smad 2 and Smad3 whereas Alk-1 phosphorylates Smad1 (Smad5 and Smad8, also activated by Alk-1, are not illustrated). The receptor Smads then complex with Co-Smad4 resulting in their transport to the nucleus where they cooperate with other factors to regulate transcription of critical genes, here represented by CTGF and α2(I) collagen. Also illustrated is a non-canonical pathway resulting in the activation of c-Abl. As pictured, imatinib blocks the activity of c-Abl, effectively inhibiting the fibrotic response although the events downstream of c-Abl are presently unknown. Imatinib also blocks the phosphorylation of Smad1, but here also the pathway is unknown.
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