Anti-EMT and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model. (31st December 2022)

• Record Type: Journal Article
• Authors: Chang, Yu-Teng; Chung, Mu-Chi; Chang, Chi-Hao; Chiu, Kuan-Hsun; Shieh, Jeng-Jer; Wu, Ming-Ju
• Is Part Of: Pharmaceutical biology. Volume 60:Number 1(2022)
• Page Start: 1198
• Page End: 1206
• Publication Date: 2022-12-31
• Subjects: Epithelial–mesenchymal transition -- renal fibrosis -- unilateral ureteral obstruction; Pharmacognosy -- Periodicals; Materia medica, Vegetable -- Periodicals; 615.321
• DOI: 10.1080/13880209.2022.2088809
• Languages: English
• ISSNs: 1388-0209

Abstract

Abstract: 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-β1 (TGF-β1), followed by treatment with 1 and 5 μM 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 μM in NRK-52E cells, and no significant difference at concentrations less than 5 μM. PCA ameliorated TGF-β1-induced EMT, such as enhanced E-cadherin and decreased vimentin. Fibrotic markers collagen IV and α-smooth muscle actin (α-SMA) increased in TGF-β1-induced NRK-52E. Moreover, PCA reduced TGF-β1-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 α-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-β1-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.