Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/HO-1 Pathway
Background Diabetic nephropathy (DN) is the most common and serious complication of diabetes mellitus. Shionone (SH), an important triterpenoid compound in the root extract of Aster, might exert a protective effect in DN mice and high glucose cultivated glomerular podocytes. The current study aimed...
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Korean Diabetes Association
2025-01-01
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| Series: | Diabetes & Metabolism Journal |
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| Online Access: | http://e-dmj.org/upload/pdf/dmj-2024-0024.pdf |
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| author | Tian Xiao Hanzhen Zhao Yucong Wang Mengyin Chen Cong Wang Chen Qiao |
| author_facet | Tian Xiao Hanzhen Zhao Yucong Wang Mengyin Chen Cong Wang Chen Qiao |
| author_sort | Tian Xiao |
| collection | DOAJ |
| description | Background Diabetic nephropathy (DN) is the most common and serious complication of diabetes mellitus. Shionone (SH), an important triterpenoid compound in the root extract of Aster, might exert a protective effect in DN mice and high glucose cultivated glomerular podocytes. The current study aimed to unravel the underlying mechanism by which SH mitigates DN. We postulate that SH stimulates the expression of sestrin-2 (SESN2), a pivotal stress-inducible protein in the anti-inflammasome machinery. Methods We utilized high-fat diet combined with streptozotocin (55 mg/kg intraperitoneal) for DN mice model, and high glucose (30 mM, 48 hours) cultured glomerular podocytes for DN cell model to evaluate the effect of SH. We also preformed experimentation on SESN2 deficiency models (SESN2 knockout mice and SESN2 siRNA in cells) to further prove our hypothesis. Results The results demonstrated that SH effectively suppressed glomerular fibrosis, induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and inhibited NLR family pyrin domain containing 3 (NLRP3) activation. Furthermore, our findings revealed that SH exerted its anti-inflammatory effect through Sesn2-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and subsequent activation of its downstream target heme oxygenase-1 (HO-1). Conclusion In summary, our findings suggest that SH serves as a promising therapeutic agent for the treatment of DN-related glomerular fibrosis. SH enhances the expression of SESN2, attenuates α-smooth muscle actin accumulation, and suppresses NLRP3-related inflammation through the Nrf2/HO-1 signaling pathway. |
| format | Article |
| id | doaj-art-9a8a8b3615704001a283e0ac1d3fa0e8 |
| institution | Kabale University |
| issn | 2233-6079 2233-6087 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Korean Diabetes Association |
| record_format | Article |
| series | Diabetes & Metabolism Journal |
| spelling | doaj-art-9a8a8b3615704001a283e0ac1d3fa0e82025-01-15T07:46:19ZengKorean Diabetes AssociationDiabetes & Metabolism Journal2233-60792233-60872025-01-01491344810.4093/dmj.2024.00242871Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/HO-1 PathwayTian Xiao0Hanzhen Zhao1Yucong Wang2Mengyin Chen3Cong Wang4Chen Qiao5 China Pharmaceutical University, Nanjing, China China Pharmaceutical University, Nanjing, China School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China Department of Pharmacology, Nanjing Medical University, Nanjing, China School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaBackground Diabetic nephropathy (DN) is the most common and serious complication of diabetes mellitus. Shionone (SH), an important triterpenoid compound in the root extract of Aster, might exert a protective effect in DN mice and high glucose cultivated glomerular podocytes. The current study aimed to unravel the underlying mechanism by which SH mitigates DN. We postulate that SH stimulates the expression of sestrin-2 (SESN2), a pivotal stress-inducible protein in the anti-inflammasome machinery. Methods We utilized high-fat diet combined with streptozotocin (55 mg/kg intraperitoneal) for DN mice model, and high glucose (30 mM, 48 hours) cultured glomerular podocytes for DN cell model to evaluate the effect of SH. We also preformed experimentation on SESN2 deficiency models (SESN2 knockout mice and SESN2 siRNA in cells) to further prove our hypothesis. Results The results demonstrated that SH effectively suppressed glomerular fibrosis, induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and inhibited NLR family pyrin domain containing 3 (NLRP3) activation. Furthermore, our findings revealed that SH exerted its anti-inflammatory effect through Sesn2-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and subsequent activation of its downstream target heme oxygenase-1 (HO-1). Conclusion In summary, our findings suggest that SH serves as a promising therapeutic agent for the treatment of DN-related glomerular fibrosis. SH enhances the expression of SESN2, attenuates α-smooth muscle actin accumulation, and suppresses NLRP3-related inflammation through the Nrf2/HO-1 signaling pathway.http://e-dmj.org/upload/pdf/dmj-2024-0024.pdfnlr family, pyrin domain-containing 3 proteinsesn 2 proteinshionone |
| spellingShingle | Tian Xiao Hanzhen Zhao Yucong Wang Mengyin Chen Cong Wang Chen Qiao Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/HO-1 Pathway Diabetes & Metabolism Journal nlr family, pyrin domain-containing 3 protein sesn 2 protein shionone |
| title | Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/HO-1 Pathway |
| title_full | Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/HO-1 Pathway |
| title_fullStr | Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/HO-1 Pathway |
| title_full_unstemmed | Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/HO-1 Pathway |
| title_short | Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/HO-1 Pathway |
| title_sort | shionone inhibits glomerular fibirosis by suppressing nlrp3 related inflammasome though sesn2 nrf2 ho 1 pathway |
| topic | nlr family, pyrin domain-containing 3 protein sesn 2 protein shionone |
| url | http://e-dmj.org/upload/pdf/dmj-2024-0024.pdf |
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