Fig. 5 | Signal Transduction and Targeted Therapy

Fig. 5

From: Targeting fibrosis: mechanisms and clinical trials

Fig. 5

Overview of canonical TGF-β/Smad signaling pathway. Various cytokines stimulate the transcipiton of TGF-β, such as PDGFs, TGF-βs, TNF-α, IL-1β, and EGF. Pro-TGF-β is synthesized in the ribosome and endoplasmic reticulum. After dimeration, LAP binds to mature TGF-β and attaches to LTBP, entering the intercellular space through exocytosis. Actived TGF-β is released by proteases, and binds to TGFβR2 and TGFβR1. Phosphorylated TGFβR2 phosphorylates TGFβR1. TGFβR1 subsequently triggers the phosphorylation of Smad2/3, which interact with Smad4 and enter the nucleus to activate the expression of target genes. Smad7 is a negative regulator of TGF-β/Smad signaling. LAP, latency-associated peptide; LTBP, latent TGF-β binding protein

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