miR-154-5p Affects the TGFβ1/Smad3 Pathway on the Fibrosis of Diabetic Kidney Disease via Binding E3 Ubiquitin Ligase Smurf1

Figure 8

Possible mechanism. In the normal glucose state, TGFβ1 activates TRI and TRII in small amounts, causing phosphorylated Smad2 and Smad3 to bind Smad4 as polymers, which enter the nucleus and participate in transcriptional regulation of fibrosis. Smurf1 inhibits TGFβ1 signaling by regulating the classical pathway of Smad3 through TRI ubiquitination (Ub) via Smad7 or directly through the potential pathway of Smad3 ubiquitination. In the high glucose state, TGFβ1/Smads pathway increases activation, causing more miR-154-5p to inhibit Smurf1, thus indirectly promoting TGFβ1/Smads pathway activation and promoting the renal fibrosis process. The effect of lentivirus for the inhibitor of miR-154-5p can block this reaction thus indirectly alleviating diabetic kidney disease.