FIGURE 1.

Canonical TGF-β/Smad pathway. TGF-β synthesized in precursor form combines with latency-associated peptide (LAP) that promotes attachment with LTBP through the formation of disulfide bonds, which is released from the LAP and LTBP and becomes active when exposed to various stimuli. The active TGF-β binds to TGFβRII, which recruits and activates TGFβRI through phosphorylated the GS domain in TGFβRI. TGFβRI phosphorylates and activates Smad2 and Smad3 (R-Smads). Smad4 combined with phosphorylated R-Smads to form a trimer complex for transcriptional regulation. Smad7 is involved and acts as a negative feedback regulation loop to regulate the target genes that regulate cell homeostasis.