Chrysophanol-mediated trx-1 activation attenuates renal fibrosis through inhibition of the JNK/Cx43 signaling pathway
Purpose This study aimed to investigate the inhibitory effect of chrysophanol on renal fibrosis and its molecular mechanism.Methods Initially, potential targets of chrysophanol were predicted through network pharmacology analysis, and a protein-protein interaction network of these targets was constr...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2398710 |
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| author | Neng Bao Jin Wang Qiyu Yue Fang Cao Xuejing Gu Kejian Wen Wei Kong Mingjia Gu |
| author_facet | Neng Bao Jin Wang Qiyu Yue Fang Cao Xuejing Gu Kejian Wen Wei Kong Mingjia Gu |
| author_sort | Neng Bao |
| collection | DOAJ |
| description | Purpose This study aimed to investigate the inhibitory effect of chrysophanol on renal fibrosis and its molecular mechanism.Methods Initially, potential targets of chrysophanol were predicted through network pharmacology analysis, and a protein-protein interaction network of these targets was constructed using Venn diagrams and the STRING database. GO enrichment analysis predicted the biological process of chrysophanol in treating renal fibrosis. Subsequently, both in vivo and in vitro experiments were conducted using unilateral ureteral obstruction (UUO) induced CKD mouse model and HK-2 cell model, respectively. In the mouse model, different doses of chrysophanol were administered to assess its renal protective effects through biochemical indicators, histological examination, and immunofluorescence staining. In the cell model, the regulatory effect of chrysophanol on the Trx-1/JNK/Cx43 pathway was evaluated using western blotting and flow cytometry.Results Chrysophanol treatment significantly ameliorated renal dysfunction and histopathological damage in the UUO mouse model, accompanied by a reduction in serum oxidative stress markers. Furthermore, chrysophanol markedly upregulated the expression of Trx-1 in renal tissues and inhibited the activation of the JNK/Cx43 signaling pathway. At the cellular level, chrysophanol enhanced the activity of Trx-1 and downregulated the JNK/Cx43 signaling pathway, thereby inhibiting TGF-β induced oxidative stress and cell apoptosis.Conclusion This study demonstrated a significant inhibitory effect of chrysophanol on renal fibrosis, mediated by the activation of Trx-1 to inhibit the JNK/Cx43 pathway. These findings provide experimental support for the potential use of chrysophanol as a therapeutic agent for renal fibrosis. |
| format | Article |
| id | doaj-art-e4f18bec259e4c408f271a63328fffba |
| institution | OA Journals |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-e4f18bec259e4c408f271a63328fffba2025-08-20T02:38:11ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2398710Chrysophanol-mediated trx-1 activation attenuates renal fibrosis through inhibition of the JNK/Cx43 signaling pathwayNeng Bao0Jin Wang1Qiyu Yue2Fang Cao3Xuejing Gu4Kejian Wen5Wei Kong6Mingjia Gu7Department of Nephrology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing city, Jiangsu, ChinaDepartment of Gastroenterology, Affiliated Hospital of Jiangnan University, Jiangsu, ChinaSchool of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu, ChinaDepartment of Nephrology, Changshu Hospital affiliated to Nanjing University of Chinese Medicine, Changshu city, Jiangsu, ChinaDepartment of Nephrology, Changshu Hospital affiliated to Nanjing University of Chinese Medicine, Changshu city, Jiangsu, ChinaDepartment of Nephrology, Changshu Hospital affiliated to Nanjing University of Chinese Medicine, Changshu city, Jiangsu, ChinaDepartment of Nephrology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing city, Jiangsu, ChinaDepartment of Nephrology, Changshu Hospital affiliated to Nanjing University of Chinese Medicine, Changshu city, Jiangsu, ChinaPurpose This study aimed to investigate the inhibitory effect of chrysophanol on renal fibrosis and its molecular mechanism.Methods Initially, potential targets of chrysophanol were predicted through network pharmacology analysis, and a protein-protein interaction network of these targets was constructed using Venn diagrams and the STRING database. GO enrichment analysis predicted the biological process of chrysophanol in treating renal fibrosis. Subsequently, both in vivo and in vitro experiments were conducted using unilateral ureteral obstruction (UUO) induced CKD mouse model and HK-2 cell model, respectively. In the mouse model, different doses of chrysophanol were administered to assess its renal protective effects through biochemical indicators, histological examination, and immunofluorescence staining. In the cell model, the regulatory effect of chrysophanol on the Trx-1/JNK/Cx43 pathway was evaluated using western blotting and flow cytometry.Results Chrysophanol treatment significantly ameliorated renal dysfunction and histopathological damage in the UUO mouse model, accompanied by a reduction in serum oxidative stress markers. Furthermore, chrysophanol markedly upregulated the expression of Trx-1 in renal tissues and inhibited the activation of the JNK/Cx43 signaling pathway. At the cellular level, chrysophanol enhanced the activity of Trx-1 and downregulated the JNK/Cx43 signaling pathway, thereby inhibiting TGF-β induced oxidative stress and cell apoptosis.Conclusion This study demonstrated a significant inhibitory effect of chrysophanol on renal fibrosis, mediated by the activation of Trx-1 to inhibit the JNK/Cx43 pathway. These findings provide experimental support for the potential use of chrysophanol as a therapeutic agent for renal fibrosis.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2398710Chronic kidney diseasechrysophanolrenal fibrosisTrx-1JNKCx43 |
| spellingShingle | Neng Bao Jin Wang Qiyu Yue Fang Cao Xuejing Gu Kejian Wen Wei Kong Mingjia Gu Chrysophanol-mediated trx-1 activation attenuates renal fibrosis through inhibition of the JNK/Cx43 signaling pathway Renal Failure Chronic kidney disease chrysophanol renal fibrosis Trx-1 JNK Cx43 |
| title | Chrysophanol-mediated trx-1 activation attenuates renal fibrosis through inhibition of the JNK/Cx43 signaling pathway |
| title_full | Chrysophanol-mediated trx-1 activation attenuates renal fibrosis through inhibition of the JNK/Cx43 signaling pathway |
| title_fullStr | Chrysophanol-mediated trx-1 activation attenuates renal fibrosis through inhibition of the JNK/Cx43 signaling pathway |
| title_full_unstemmed | Chrysophanol-mediated trx-1 activation attenuates renal fibrosis through inhibition of the JNK/Cx43 signaling pathway |
| title_short | Chrysophanol-mediated trx-1 activation attenuates renal fibrosis through inhibition of the JNK/Cx43 signaling pathway |
| title_sort | chrysophanol mediated trx 1 activation attenuates renal fibrosis through inhibition of the jnk cx43 signaling pathway |
| topic | Chronic kidney disease chrysophanol renal fibrosis Trx-1 JNK Cx43 |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2398710 |
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