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Transcriptional profile changes after treatment of ischemia reperfusion injury-induced kidney fibrosis with 18β-glycyrrhetinic acid
INTRODUCTION: Chronic kidney disease (CKD) is characterized by renal fibrosis without effective therapy. 18β-Glycyrrhetinic acid (GA) is reported to have detoxification and anti-inflammatory functions and promotes tissue repair. However, the role of GA in CKD remains unclear. In this study, we inves...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225714/ https://www.ncbi.nlm.nih.gov/pubmed/35699239 http://dx.doi.org/10.1080/0886022X.2022.2061998 |
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author | Jiang, Yamei Cai, Chengzhe Zhang, Pingbao Luo, Yongsheng Guo, Jingjing Li, Jiawei Rong, Ruiming Zhang, Yi Zhu, Tongyu |
author_facet | Jiang, Yamei Cai, Chengzhe Zhang, Pingbao Luo, Yongsheng Guo, Jingjing Li, Jiawei Rong, Ruiming Zhang, Yi Zhu, Tongyu |
author_sort | Jiang, Yamei |
collection | PubMed |
description | INTRODUCTION: Chronic kidney disease (CKD) is characterized by renal fibrosis without effective therapy. 18β-Glycyrrhetinic acid (GA) is reported to have detoxification and anti-inflammatory functions and promotes tissue repair. However, the role of GA in CKD remains unclear. In this study, we investigated whether GA has a potential therapeutic effect in kidney fibrosis. METHODS: A renal fibrosis mouse model was established by ischemia/reperfusion (I/R) injury via clamping unilateral left renal pedicle for 45 min; then, the mice were treated with vehicle or GA. Kidney tissues and blood samples were extracted 14 days after reperfusion and renal function, histopathological staining, quantitative PCR, and western blotting were performed. RNA-seq was performed to explore the changes in the transcriptional profile after GA treatment. RESULTS: Renal function, pathological and molecular analysis displayed that fibrosis was successfully induced in the I/R model. In the GA treatment group, the severity of fibrosis gradually reduced with the best effect seen at a concentration of 25 mg kg (−1). A total of 970 differentially expressed genes were identified. Pathway enrichment showed that reduced activation and migration of inflammatory cells and decreased chemokine interaction in significant pathways. Protein–protein interaction networks were constructed and 15 hub genes were selected by degree rank, including chemokines, such as C3, Ccl6, Ccr2, Ptafr, Timp1, and Pf4. CONCLUSIONS: GA may alleviate renal fibrosis by inhibiting the inflammatory response. GA is a promising therapy that may perhaps be used in treating renal fibrosis and CKD. |
format | Online Article Text |
id | pubmed-9225714 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-92257142022-06-24 Transcriptional profile changes after treatment of ischemia reperfusion injury-induced kidney fibrosis with 18β-glycyrrhetinic acid Jiang, Yamei Cai, Chengzhe Zhang, Pingbao Luo, Yongsheng Guo, Jingjing Li, Jiawei Rong, Ruiming Zhang, Yi Zhu, Tongyu Ren Fail Laboratory Study INTRODUCTION: Chronic kidney disease (CKD) is characterized by renal fibrosis without effective therapy. 18β-Glycyrrhetinic acid (GA) is reported to have detoxification and anti-inflammatory functions and promotes tissue repair. However, the role of GA in CKD remains unclear. In this study, we investigated whether GA has a potential therapeutic effect in kidney fibrosis. METHODS: A renal fibrosis mouse model was established by ischemia/reperfusion (I/R) injury via clamping unilateral left renal pedicle for 45 min; then, the mice were treated with vehicle or GA. Kidney tissues and blood samples were extracted 14 days after reperfusion and renal function, histopathological staining, quantitative PCR, and western blotting were performed. RNA-seq was performed to explore the changes in the transcriptional profile after GA treatment. RESULTS: Renal function, pathological and molecular analysis displayed that fibrosis was successfully induced in the I/R model. In the GA treatment group, the severity of fibrosis gradually reduced with the best effect seen at a concentration of 25 mg kg (−1). A total of 970 differentially expressed genes were identified. Pathway enrichment showed that reduced activation and migration of inflammatory cells and decreased chemokine interaction in significant pathways. Protein–protein interaction networks were constructed and 15 hub genes were selected by degree rank, including chemokines, such as C3, Ccl6, Ccr2, Ptafr, Timp1, and Pf4. CONCLUSIONS: GA may alleviate renal fibrosis by inhibiting the inflammatory response. GA is a promising therapy that may perhaps be used in treating renal fibrosis and CKD. Taylor & Francis 2022-06-14 /pmc/articles/PMC9225714/ /pubmed/35699239 http://dx.doi.org/10.1080/0886022X.2022.2061998 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 | Laboratory Study Jiang, Yamei Cai, Chengzhe Zhang, Pingbao Luo, Yongsheng Guo, Jingjing Li, Jiawei Rong, Ruiming Zhang, Yi Zhu, Tongyu Transcriptional profile changes after treatment of ischemia reperfusion injury-induced kidney fibrosis with 18β-glycyrrhetinic acid |
title | Transcriptional profile changes after treatment of ischemia reperfusion injury-induced kidney fibrosis with 18β-glycyrrhetinic acid |
title_full | Transcriptional profile changes after treatment of ischemia reperfusion injury-induced kidney fibrosis with 18β-glycyrrhetinic acid |
title_fullStr | Transcriptional profile changes after treatment of ischemia reperfusion injury-induced kidney fibrosis with 18β-glycyrrhetinic acid |
title_full_unstemmed | Transcriptional profile changes after treatment of ischemia reperfusion injury-induced kidney fibrosis with 18β-glycyrrhetinic acid |
title_short | Transcriptional profile changes after treatment of ischemia reperfusion injury-induced kidney fibrosis with 18β-glycyrrhetinic acid |
title_sort | transcriptional profile changes after treatment of ischemia reperfusion injury-induced kidney fibrosis with 18β-glycyrrhetinic acid |
topic | Laboratory Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225714/ https://www.ncbi.nlm.nih.gov/pubmed/35699239 http://dx.doi.org/10.1080/0886022X.2022.2061998 |
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