Integrin 86 mediates epithelial-mesenchymal transition in diabetic kidney disease

The progression of diabetic kidney disease (DKD) is associated with increased fibronectin (FN) levels in proximal tubular epithelial cells. Bioinformatics analysis showed that integrin 86 and cell adhesion function were significantly changed in the cortices of db/db mice. Remodelling of cell adhesion is one of the core changes during epithelial-mesenchymal transition (EMT) in DKD. Integrin is a family of transmembrane proteins that regulates cell adhesion and migration, and extracellular FN is the major ligand of integrin 86. We found that the expression of integrin 86 was elevated in the proximal tubules of db/db mice and FN-induced renal proximal tubule cells. The levels of EMT were also significantly increased in vivo and in vitro. In addition, FN treatment activated the Fak/Src pathway, increased the expression of p-YAP, and then upregulated the Notch1 pathway in diabetic proximal tubules. Knockdown of integrin 86 or Notch1 reduced the EMT aggravation induced by FN. Furthermore, urinary integrin 86 was significantly increased in DKD patients. Our findings reveal a critical role of integrin 86 in regulating EMT in proximal tubular epithelial cells and identify a novel direction for the detection and treatment of DKD.

Automated summary

The progression of diabetic kidney disease (DKD) is associated with increased fibronectin (FN) levels in proximal tubular epithelial cells. Remodelling of cell adhesion in DKD is closely related to epithelial-mesenchymal transition (EMT). Integrin 86, a transmembrane protein that regulates cell adhesion and migration, and its ligand FN play significant roles in DKD. The expression of integrin 86 and EMT are elevated in DKD, and their aggravation can be reduced by knockdown of integrin 86 or Notch1. Furthermore, urinary integrin 86 is significantly increased in DKD patients.