Anti-EMT and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model

Context Protocatechuic aldehyde (PCA) is a natural product that has various benefits for fibrosis. Objective This study evaluated the effects of PCA on renal fibrosis. Materials and methods Epithelial-mesenchymal transition (EMT) was induced by 20 ng/mL transforming growth factor-beta 1 (TGF-beta 1), followed by treatment with 1 and 5 mu M PCA, in the rat renal proximal tubular cell line NRK-52E. Cell viability, protein expression, and scratch wound-healing assays were conducted. Sprague-Dawley (SD) rats underwent unilateral ureteral obstruction (UUO) surgery for renal fibrosis indication and were treated with 50 and 100 mg/kg PCA for 14 days. Results The IC50 of PCA was appropriately 13.75 +/- 1.91 mu M in NRK-52E cells, and no significant difference at concentrations less than 5 mu M. PCA ameliorated TGF-beta 1-induced EMT, such as enhanced E-cadherin and decreased vimentin. Fibrotic markers collagen IV and alpha-smooth muscle actin (alpha-SMA) increased in TGF-beta 1-induced NRK-52E. Moreover, PCA reduced TGF-beta 1-induced migration in the wound-healing assay. Analysis of rat kidneys indicated that PCA reduced UUO-induced hydronephrosis (control: 15.11 +/- 1.00%; UUO: 39.89 +/- 1.91%; UUO + PCA50: 18.37 +/- 1.61%; UUO + PCA100: 17.67 +/- 1.39%). Protein level demonstrated that PCA not only decreased vimentin expression and enhanced E-cadherin expression, but inhibited UUO-induced collagen IV and alpha-SMA upregulation, indicating that it could mitigate EMT in a rat model of UUO-induced renal fibrosis. Discussion and conclusions This study suggested that PCA decreases TGF-beta 1-induced fibrosis and EMT in vitro and in vivo. These findings demonstrate pharmacological effects of PCA and might be a potential strategy for the prevention of organ fibrosis in clinics.

Automated summary

This study evaluated the effects of protocatechuic aldehyde (PCA) on renal fibrosis. The results showed that PCA could inhibit TGF-beta 1-induced fibrosis and EMT, suggesting it as a potential strategy for preventing organ fibrosis in clinics.