Activation of sclerostin inhibits Isg20-Mediated aerobic glycolysis ameliorating renal Fibrosis: the renoprotective mechanism of hederagenin in CKD
Sclerostin (Sost) functions as an inhibitor of the Wnt/β-catenin signaling pathway, which is known to promote kidney cell epithelial-to-mesenchymal transition (EMT), and fibrosis in chronic kidney disease (CKD). However, the renoprotective effects of Sost in kidney diseases and its therapeutic poten...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
|
| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725002757 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839631240952545280 |
|---|---|
| author | Rang-yue Han Rui-zhi Tan Ling-hui Xu Jing-yi Lin Tong Li Hong-wei Su Ping Li Peng Liu Hui-yao Lan Li Wang |
| author_facet | Rang-yue Han Rui-zhi Tan Ling-hui Xu Jing-yi Lin Tong Li Hong-wei Su Ping Li Peng Liu Hui-yao Lan Li Wang |
| author_sort | Rang-yue Han |
| collection | DOAJ |
| description | Sclerostin (Sost) functions as an inhibitor of the Wnt/β-catenin signaling pathway, which is known to promote kidney cell epithelial-to-mesenchymal transition (EMT), and fibrosis in chronic kidney disease (CKD). However, the renoprotective effects of Sost in kidney diseases and its therapeutic potential as a target remain unknown. To clarify the protective role of Sost in CKD kidneys, we utilized ultrasound microbubble-mediated renal in situ gene transfection to overexpress and knockdown Sost in kidney. Subsequently, we employed the TurboID-based protein interaction technique to screen for Sost-binding proteins and combined it with ECAR/OCR to elucidate the regulation of glycolytic pathways by Sost and its binding proteins. Sost is predominantly expressed in renal tubules and that its expression is significantly diminished in renal tissues of CKD patients, as well as in UUO and folic acid (FA) induced CKD mouse. Overexpression of Sost in vivo and in vitro ameliorated tubular injury and fibrosis. Employing the TurboID technique, we uncovered an interaction between Sost and the potential glycolysis-associated protein Isg20, an interferon-stimulated ribonuclease. This binding interaction serves to inhibit Isg20-mediated aerobic glycolysis and subsequent fibrosis within the kidney of CKD. For Sost agonists screening, we found that HDG exerts salient anti-fibrotic and renal protective effects in CKD, which are likely attributable to its significant upregulation of Sost expression, thereby inhibiting Isg20-mediated glycolysis. In summary, we demonstrate that upregulation of Sost by HDG inhibits glycolysis and renal fibrosis in CKD through binding and suppressing of Isg20, and targeting Sost may develop novel approaches to treat CKD. |
| format | Article |
| id | doaj-art-f415bd4e08764347a1036fc0e456f75c |
| institution | Matheson Library |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-f415bd4e08764347a1036fc0e456f75c2025-07-12T04:46:15ZengElsevierRedox Biology2213-23172025-09-0185103762Activation of sclerostin inhibits Isg20-Mediated aerobic glycolysis ameliorating renal Fibrosis: the renoprotective mechanism of hederagenin in CKDRang-yue Han0Rui-zhi Tan1Ling-hui Xu2Jing-yi Lin3Tong Li4Hong-wei Su5Ping Li6Peng Liu7Hui-yao Lan8Li Wang9Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, ChinaResearch Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China; Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, 646000, ChinaResearch Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, ChinaResearch Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, ChinaResearch Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, ChinaDepartment of Urology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, ChinaBeijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, 100029, ChinaXiyuan Hospital, China Academy of Chinese Medicine Sciences, Beijing, 100091, China; Corresponding author. No.1 Xiyuan playground Road, Beijing, China.Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China; Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, 999077, China; Corresponding author. Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong, Hong Kong, China.Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China; Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, 646000, China; Corresponding author. Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.Sclerostin (Sost) functions as an inhibitor of the Wnt/β-catenin signaling pathway, which is known to promote kidney cell epithelial-to-mesenchymal transition (EMT), and fibrosis in chronic kidney disease (CKD). However, the renoprotective effects of Sost in kidney diseases and its therapeutic potential as a target remain unknown. To clarify the protective role of Sost in CKD kidneys, we utilized ultrasound microbubble-mediated renal in situ gene transfection to overexpress and knockdown Sost in kidney. Subsequently, we employed the TurboID-based protein interaction technique to screen for Sost-binding proteins and combined it with ECAR/OCR to elucidate the regulation of glycolytic pathways by Sost and its binding proteins. Sost is predominantly expressed in renal tubules and that its expression is significantly diminished in renal tissues of CKD patients, as well as in UUO and folic acid (FA) induced CKD mouse. Overexpression of Sost in vivo and in vitro ameliorated tubular injury and fibrosis. Employing the TurboID technique, we uncovered an interaction between Sost and the potential glycolysis-associated protein Isg20, an interferon-stimulated ribonuclease. This binding interaction serves to inhibit Isg20-mediated aerobic glycolysis and subsequent fibrosis within the kidney of CKD. For Sost agonists screening, we found that HDG exerts salient anti-fibrotic and renal protective effects in CKD, which are likely attributable to its significant upregulation of Sost expression, thereby inhibiting Isg20-mediated glycolysis. In summary, we demonstrate that upregulation of Sost by HDG inhibits glycolysis and renal fibrosis in CKD through binding and suppressing of Isg20, and targeting Sost may develop novel approaches to treat CKD.http://www.sciencedirect.com/science/article/pii/S2213231725002757CKDFibrosisIsg20SostHederagenin |
| spellingShingle | Rang-yue Han Rui-zhi Tan Ling-hui Xu Jing-yi Lin Tong Li Hong-wei Su Ping Li Peng Liu Hui-yao Lan Li Wang Activation of sclerostin inhibits Isg20-Mediated aerobic glycolysis ameliorating renal Fibrosis: the renoprotective mechanism of hederagenin in CKD Redox Biology CKD Fibrosis Isg20 Sost Hederagenin |
| title | Activation of sclerostin inhibits Isg20-Mediated aerobic glycolysis ameliorating renal Fibrosis: the renoprotective mechanism of hederagenin in CKD |
| title_full | Activation of sclerostin inhibits Isg20-Mediated aerobic glycolysis ameliorating renal Fibrosis: the renoprotective mechanism of hederagenin in CKD |
| title_fullStr | Activation of sclerostin inhibits Isg20-Mediated aerobic glycolysis ameliorating renal Fibrosis: the renoprotective mechanism of hederagenin in CKD |
| title_full_unstemmed | Activation of sclerostin inhibits Isg20-Mediated aerobic glycolysis ameliorating renal Fibrosis: the renoprotective mechanism of hederagenin in CKD |
| title_short | Activation of sclerostin inhibits Isg20-Mediated aerobic glycolysis ameliorating renal Fibrosis: the renoprotective mechanism of hederagenin in CKD |
| title_sort | activation of sclerostin inhibits isg20 mediated aerobic glycolysis ameliorating renal fibrosis the renoprotective mechanism of hederagenin in ckd |
| topic | CKD Fibrosis Isg20 Sost Hederagenin |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725002757 |
| work_keys_str_mv | AT rangyuehan activationofsclerostininhibitsisg20mediatedaerobicglycolysisamelioratingrenalfibrosistherenoprotectivemechanismofhederagenininckd AT ruizhitan activationofsclerostininhibitsisg20mediatedaerobicglycolysisamelioratingrenalfibrosistherenoprotectivemechanismofhederagenininckd AT linghuixu activationofsclerostininhibitsisg20mediatedaerobicglycolysisamelioratingrenalfibrosistherenoprotectivemechanismofhederagenininckd AT jingyilin activationofsclerostininhibitsisg20mediatedaerobicglycolysisamelioratingrenalfibrosistherenoprotectivemechanismofhederagenininckd AT tongli activationofsclerostininhibitsisg20mediatedaerobicglycolysisamelioratingrenalfibrosistherenoprotectivemechanismofhederagenininckd AT hongweisu activationofsclerostininhibitsisg20mediatedaerobicglycolysisamelioratingrenalfibrosistherenoprotectivemechanismofhederagenininckd AT pingli activationofsclerostininhibitsisg20mediatedaerobicglycolysisamelioratingrenalfibrosistherenoprotectivemechanismofhederagenininckd AT pengliu activationofsclerostininhibitsisg20mediatedaerobicglycolysisamelioratingrenalfibrosistherenoprotectivemechanismofhederagenininckd AT huiyaolan activationofsclerostininhibitsisg20mediatedaerobicglycolysisamelioratingrenalfibrosistherenoprotectivemechanismofhederagenininckd AT liwang activationofsclerostininhibitsisg20mediatedaerobicglycolysisamelioratingrenalfibrosistherenoprotectivemechanismofhederagenininckd |