Anti-EMT and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model.
Pharm Biol
; 60(1): 1198-1206, 2022 Dec.
Article
em En
| MEDLINE
| ID: mdl-35758295
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 ANDMETHODS:
Epithelial-mesenchymal transition (EMT) was induced by 20 ng/mL transforming growth factor-ß1 (TGF-ß1), 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-ß1-induced EMT, such as enhanced E-cadherin and decreased vimentin. Fibrotic markers collagen IV and α-smooth muscle actin (α-SMA) increased in TGF-ß1-induced NRK-52E. Moreover, PCA reduced TGF-ß1-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 ANDCONCLUSIONS:
This study suggested that PCA decreases TGF-ß1-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Obstrução Ureteral
/
Nefropatias
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Pharm Biol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Taiwan