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Activated TGF-1 binds to TGF- receptors I/II, phosphorylates mothers against decapentaplegic homolog 2/3 (Smad2/3), forms a complex with Smad4, and translocates to the nucleus, thereby directly inducing the transcription of fibrosis-related genes, such as collagen I/III, fibronectin, and -SMA (Kim et al