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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-β1 (TGF-β1), fol...

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Autores principales: Chang, Yu-Teng, Chung, Mu-Chi, Chang, Chi-Hao, Chiu, Kuan-Hsun, Shieh, Jeng-Jer, Wu, Ming-Ju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9477482/
https://www.ncbi.nlm.nih.gov/pubmed/35758295
http://dx.doi.org/10.1080/13880209.2022.2088809
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author Chang, Yu-Teng
Chung, Mu-Chi
Chang, Chi-Hao
Chiu, Kuan-Hsun
Shieh, Jeng-Jer
Wu, Ming-Ju
author_facet Chang, Yu-Teng
Chung, Mu-Chi
Chang, Chi-Hao
Chiu, Kuan-Hsun
Shieh, Jeng-Jer
Wu, Ming-Ju
author_sort Chang, Yu-Teng
collection PubMed
description 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 IC(50) 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.
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spelling pubmed-94774822022-09-16 Anti-EMT and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model Chang, Yu-Teng Chung, Mu-Chi Chang, Chi-Hao Chiu, Kuan-Hsun Shieh, Jeng-Jer Wu, Ming-Ju Pharm Biol Research Article 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 IC(50) 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. Taylor & Francis 2022-06-25 /pmc/articles/PMC9477482/ /pubmed/35758295 http://dx.doi.org/10.1080/13880209.2022.2088809 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chang, Yu-Teng
Chung, Mu-Chi
Chang, Chi-Hao
Chiu, Kuan-Hsun
Shieh, Jeng-Jer
Wu, Ming-Ju
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
title_full Anti-EMT and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model
title_fullStr Anti-EMT and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model
title_full_unstemmed Anti-EMT and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model
title_short Anti-EMT and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model
title_sort anti-emt and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9477482/
https://www.ncbi.nlm.nih.gov/pubmed/35758295
http://dx.doi.org/10.1080/13880209.2022.2088809
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