Anti-EMT and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model
| Title: | Anti-EMT and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model |
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| Authors: | Yu-Teng Chang, Mu-Chi Chung, Chi-Hao Chang, Kuan-Hsun Chiu, Jeng-Jer Shieh, Ming-Ju Wu |
| Source: | Pharmaceutical Biology, Vol 60, Iss 1, Pp 1198-1206 (2022) |
| Publisher Information: | Taylor & Francis Group, 2022. |
| Publication Year: | 2022 |
| Collection: | LCC:Therapeutics. Pharmacology |
| Subject Terms: | Epithelial–mesenchymal transition, renal fibrosis, unilateral ureteral obstruction, Therapeutics. Pharmacology, RM1-950 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 13880209 1744-5116 1388-0209 |
| Relation: | https://doaj.org/toc/1388-0209; https://doaj.org/toc/1744-5116 |
| DOI: | 10.1080/13880209.2022.2088809 |
| Access URL: | https://doaj.org/article/ae095cfeeeff4ffcb9591d96f9d5c0a6 |
| Accession Number: | edsdoj.095cfeeeff4ffcb9591d96f9d5c0a6 |
| Database: | Directory of Open Access Journals |
| ISSN: | 13880209 17445116 |
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| DOI: | 10.1080/13880209.2022.2088809 |
| Published in: | Pharmaceutical Biology |
| Language: | English |