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"It is now clear that after binding to its receptors, TGF-beta1 activates its downstream signaling pathway, Smad 2 and Smad3, to mediate fibrosis, which is negatively regulated by Smad7, an inhibitor of TGF-beta signaling, via the ubiquitin-proteasome degradation mechanism XREF_BIBR, XREF_BIBR."