ACTA1 and renal fibrosis: Activation of TGFβR1 then phosphorylates Smad2/3, facilitating their activation and translocation into the nucleus where they bind to relevant co-factors, thereby regulating the transcription of fibrotic genes such as α-smooth muscle actin (α-SMA) and fibronectin 1 (Fn1), thus promoting renal fibrosis 14, 15.