Enhanced eNOS/nitric oxide production by nebivolol interferes with TGF-β1/Smad3 signaling and collagen I deposition in the kidney after prolonged tacrolimus administration

Tacrolimus is an effective immunosuppressant commonly used post-transplantation and in certain autoimmune diseases. However, its long-term administration is associated with renal fibrosis through transforming growth factor-beta/suppressor of mother against decapentaplegic (TGF-β/Smad) signaling that could be partly attributed to endothelial dysfunction alongside decreased nitric oxide (NO) release. Our study aimed to investigate the prospective renal anti-fibrotic effect of enhanced NO production by nebivolol against tacrolimus-stimulated TGF-β1/Smad3 signaling.