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Psoralen Alleviates Renal Fibrosis by Attenuating Inflammasome-Dependent NLRP3 Activation and Epithelial–Mesenchymal Transition in a Mouse Unilateral Ureteral Obstruction Model
The role of psoralen (PS), a major active component extracted from Psoralea corylifolia L. seed, in renal fibrosis is still unclear. Thus, the objective of this study was to evaluate the effects of PS on the development and progression of renal fibrosis induced by unilateral ureteral obstruction (UU...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487722/ https://www.ncbi.nlm.nih.gov/pubmed/37685978 http://dx.doi.org/10.3390/ijms241713171 |
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author | Lee, Tae Won Bae, Eunjin Kim, Jin Hyun Jung, Myeong Hee Park, Dong Jun |
author_facet | Lee, Tae Won Bae, Eunjin Kim, Jin Hyun Jung, Myeong Hee Park, Dong Jun |
author_sort | Lee, Tae Won |
collection | PubMed |
description | The role of psoralen (PS), a major active component extracted from Psoralea corylifolia L. seed, in renal fibrosis is still unclear. Thus, the objective of this study was to evaluate the effects of PS on the development and progression of renal fibrosis induced by unilateral ureteral obstruction (UUO) in a mouse model. Mice were divided into four groups: PS (20 mg/kg, i.g., n = 5), PS + sham (n = 5), UUO (n = 10), and PS + UUO (n = 10). PS was intragastrically administered 24 h before UUO and continued afterwards for 7 days. All mice were killed 7 days post UUO. Severe tubular atrophy, tubular injury, and tubulointerstitial fibrosis (TIF) were significantly developed in UUO mice. A higher expression of transforming growth factor-β1 (TGF-β1) was accompanied by elevated levels of α-smooth muscle actin (α-SMA) and phosphorylated Smad2/3 (pSmad2/3) at 7 days post UUO. However, PS treatment reduced tubular injury, interstitial fibrosis, and the expression levels of TGF-β1, α-SMA, and pSmad2/3. Furthermore, the levels of macrophages (represented by F4/80 positive cells) and the inflammasome, reflected by inflammasome markers such as nucleotide-binding and oligomerization domain-like receptors protein 3 (NLRP3) and cleaved caspase1 (cCASP-1), were significantly decreased by PS treatment. These results suggest that PS merits further exploration as a therapeutic agent in the management of chronic kidney disease (CKD). |
format | Online Article Text |
id | pubmed-10487722 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104877222023-09-09 Psoralen Alleviates Renal Fibrosis by Attenuating Inflammasome-Dependent NLRP3 Activation and Epithelial–Mesenchymal Transition in a Mouse Unilateral Ureteral Obstruction Model Lee, Tae Won Bae, Eunjin Kim, Jin Hyun Jung, Myeong Hee Park, Dong Jun Int J Mol Sci Article The role of psoralen (PS), a major active component extracted from Psoralea corylifolia L. seed, in renal fibrosis is still unclear. Thus, the objective of this study was to evaluate the effects of PS on the development and progression of renal fibrosis induced by unilateral ureteral obstruction (UUO) in a mouse model. Mice were divided into four groups: PS (20 mg/kg, i.g., n = 5), PS + sham (n = 5), UUO (n = 10), and PS + UUO (n = 10). PS was intragastrically administered 24 h before UUO and continued afterwards for 7 days. All mice were killed 7 days post UUO. Severe tubular atrophy, tubular injury, and tubulointerstitial fibrosis (TIF) were significantly developed in UUO mice. A higher expression of transforming growth factor-β1 (TGF-β1) was accompanied by elevated levels of α-smooth muscle actin (α-SMA) and phosphorylated Smad2/3 (pSmad2/3) at 7 days post UUO. However, PS treatment reduced tubular injury, interstitial fibrosis, and the expression levels of TGF-β1, α-SMA, and pSmad2/3. Furthermore, the levels of macrophages (represented by F4/80 positive cells) and the inflammasome, reflected by inflammasome markers such as nucleotide-binding and oligomerization domain-like receptors protein 3 (NLRP3) and cleaved caspase1 (cCASP-1), were significantly decreased by PS treatment. These results suggest that PS merits further exploration as a therapeutic agent in the management of chronic kidney disease (CKD). MDPI 2023-08-24 /pmc/articles/PMC10487722/ /pubmed/37685978 http://dx.doi.org/10.3390/ijms241713171 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lee, Tae Won Bae, Eunjin Kim, Jin Hyun Jung, Myeong Hee Park, Dong Jun Psoralen Alleviates Renal Fibrosis by Attenuating Inflammasome-Dependent NLRP3 Activation and Epithelial–Mesenchymal Transition in a Mouse Unilateral Ureteral Obstruction Model |
title | Psoralen Alleviates Renal Fibrosis by Attenuating Inflammasome-Dependent NLRP3 Activation and Epithelial–Mesenchymal Transition in a Mouse Unilateral Ureteral Obstruction Model |
title_full | Psoralen Alleviates Renal Fibrosis by Attenuating Inflammasome-Dependent NLRP3 Activation and Epithelial–Mesenchymal Transition in a Mouse Unilateral Ureteral Obstruction Model |
title_fullStr | Psoralen Alleviates Renal Fibrosis by Attenuating Inflammasome-Dependent NLRP3 Activation and Epithelial–Mesenchymal Transition in a Mouse Unilateral Ureteral Obstruction Model |
title_full_unstemmed | Psoralen Alleviates Renal Fibrosis by Attenuating Inflammasome-Dependent NLRP3 Activation and Epithelial–Mesenchymal Transition in a Mouse Unilateral Ureteral Obstruction Model |
title_short | Psoralen Alleviates Renal Fibrosis by Attenuating Inflammasome-Dependent NLRP3 Activation and Epithelial–Mesenchymal Transition in a Mouse Unilateral Ureteral Obstruction Model |
title_sort | psoralen alleviates renal fibrosis by attenuating inflammasome-dependent nlrp3 activation and epithelial–mesenchymal transition in a mouse unilateral ureteral obstruction model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487722/ https://www.ncbi.nlm.nih.gov/pubmed/37685978 http://dx.doi.org/10.3390/ijms241713171 |
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