"SB-202190 and SB-203580 deregulate TGFbeta induced Smad3 nuclear accumulation."
"Recent study demonstrate that TGFβ activate smad3 in medial smooth muscle cells, causing them to secret CTGF, which in turn stimulate adventitial fibroblasts to migrate, proliferate, produce collagen, and transform into myofibroblast [ xref ]."
"Figure XREF_FIG and Supplementary Fig. 8A show that treatment of NHDF with the selective ERK1/2 inhibitor SCH772984 31 resulted in significantly reduced SMAD3 mRNA level and reduced TGFbeta induced SMAD3 nuclear translocation, when compared to DMSO treated cells."
"Upon ligand binding by TGF-beta1, type II TGF-beta receptors (TbetaRII) activate type I TGF-beta receptors (TbetaRI), recruiting and activating the intracellular mediators Smad2 and Smad3, which subsequently complex with Smad4 before translocating to the nucleus where the complex regulate gene transcription [XREF_BIBR]."
"On the contrary, the TGF-β-activated Smad3 triggers strikingly different programs such as mesodermal differentiation in early development."
"TGF-beta induced the enrichment of Smad3 on the PAI-1 promoter, and this enrichment was abolished by STAT3C (XREF_FIG)."
"A direct cross talk between the Notch and TGF-beta signaling pathways comes from a recent study in which a direct interaction between Notch intracellular domain and Smad-3 was demonstrated, and activation of Smad-3 by TGF-beta led to an enhancement of Notch induced Hes1 gene transcription."
"The high TGF-beta expression induced by haemodynamic abnormalities during hyperfiltration may increase production of downstream molecular pathways and further production of Smad3."