EphrinB2 Ameliorates Renal Fibrosis by Inhibiting the TGF-β/Smad3 Signaling Pathway and the Inflammation Response.

BACKGROUND

EphrinB2 is known to play a variety of roles in the pathological process of fibrosis in the heart, skin, and retina, according to current research. However, the role of Ephrin- B2 in renal fibrosis remains to be clarified.

OBJECTIVE

We aimed to investigate the role of EphrinB2 in the renal fibrosis model and its underlying mechanisms.

MATERIALS AND

METHODS

Unilateral ureteral obstruction (UUO) models and TGF-β-treated renal tubular epithelial cells (HK2) were adopted in this study to determine if EphrinB2 could lead to renal fibrosis.

RESULTS

EphrinB2 was highly expressed in renal tubular cells in UUO mice. Using adeno-associated virus (AAV)-mediated EphrinB2 overexpression, we observed significant improvements in renal function and injury, as well as a marked reduction in fibrosis. For example, EphrinB2 overexpression decreased the expression of fibrosis markers such as Fibronectin and α-SMA by approximately 40%. In vitro, EphrinB2 also significantly reduced extracellular matrix (ECM) deposition and cellular fibrosis under TGF-β stimulation. Mechanistically, EphrinB2 inhibited TGF-β/Smad3 signaling by approximately 40%, and reduced inflammatory markers such as MCP1 and IL-1β by approximately 60% and 35%, respectively.

CONCLUSIONS

This study uncovered a previously unrecognized anti-fibrotic role of EphrinB2 in renal fibrosis, which is achieved through the prevention TGF-β/Smad3 signaling and inflammation response. It seemed that EphrinB2 might be a promising therapeutic target in the treatment of fibrotic diseases and kidney failure.