And, knockout of ISG15 led to decreased TGFβR1 and its downstream p-Smad2 levels, reduces transcription levels of fibrotic genes such as α-SMA, Fn1, and Vimentin, ultimately inhibited renal fibrosis (Figure 2-3 and Figure S4, S8). This evidence concerns the gene TGFBR1 and renal fibrosis.