Renal interstitial
fibrosis is a common pathway for the progression of
chronic kidney disease (CKD) to
end-stage renal disease.
Renalase, acting as a signaling molecule, has been reported to have cardiovascular and renal protective effects. However, its role in renal
fibrosis remains unknown. In this study, we evaluated the therapeutic efficacy of
renalase in rats with complete unilateral
ureteral obstruction (UUO) and examined the inhibitory effects of
renalase on transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in human proximal renal tubular epithelial (HK-2) cells. We found that in the UUO model, the expression of
renalase was markedly downregulated and adenoviral-mediated expression of
renalase significantly attenuated renal interstitial
fibrosis, as evidenced by the maintenance of
E-cadherin expression and suppressed expression of α-smooth muscle actin (α-SMA),
fibronectin and
collagen-I. In vitro,
renalase inhibited TGF-β1-mediated upregulation of α-SMA and downregulation of
E-cadherin. Increased levels of Phospho-extracellular regulated
protein kinases (p-ERK1/2) in TGF-β1-stimulated cells were reversed by
renalase cotreatment. When ERK1 was overexpressed, the inhibition of TGF-β1-induced EMT and
fibrosis mediated by
renalase was attenuated. Our study provides the first evidence that
renalase can ameliorate renal interstitial
fibrosis by suppression of tubular EMT through inhibition of the ERK pathway. These results suggest that
renalase has potential renoprotective effects in renal interstitial
fibrosis and may be an effective agent for slowing CKD progression.