The various signaling pathways involved in the fibrosis mechanism of DKD such as TGF-β1, Wnt, insulin/IGF-1, PI3K-Akt, and Janus kinase/signal transduction and transcription activation (JAK-STAT) whereas the secreted form of Klotho have an inhibitory role against it. This evidence concerns the gene TGFB1 and diabetic kidney disease.