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

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

  • Pharm Biol. 2022 Dec;60(1):1198-1206. doi: 10.1080/13880209.2022.2088809.
Yu-Teng Chang 1,  Mu-Chi Chung 2 3 4 5 6,  Chi-Hao Chang 7,  Kuan-Hsun Chiu 1,  Jeng-Jer Shieh 1 4 7,  Ming-Ju Wu 2 3 4 5 8 9
Affiliations

Affiliations

  • 1 Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
  • 2 Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
  • 3 Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
  • 4 Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
  • 5 Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
  • 6 Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan.
  • 7 Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
  • 8 School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
  • 9 Graduate Institute of Clinical Medical Sciences, School of Medicine, China Medical University, Taichung, Taiwan.
PMID: 35758295 DOI: 10.1080/13880209.2022.2088809
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.

Keywords

Epithelial–mesenchymal transition; renal fibrosis; unilateral ureteral obstruction.

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