Academic Journal
Magnolol Inhibits High Fructose-Induced Podocyte Inflammation via Downregulation of TKFC/Sp1/HDAC4/Notch1 Activation
| العنوان: | Magnolol Inhibits High Fructose-Induced Podocyte Inflammation via Downregulation of TKFC/Sp1/HDAC4/Notch1 Activation |
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| المؤلفون: | Ziang Zhou, Yumeng Wang, Yu Xing, Shuman Pan, Wanru Wang, Jie Yang, Wenyuan Wu, Jie Zhou, Luyi Huang, Qiongdan Liang, Dongmei Zhang, Lingdong Kong |
| المصدر: | Pharmaceuticals, Vol 17, Iss 11, p 1416 (2024) |
| بيانات النشر: | MDPI AG, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Pharmacy and materia medica |
| مصطلحات موضوعية: | magnolol, podocyte inflammation, TKFC, TNF-α, NICD1, high fructose, Medicine, Pharmacy and materia medica, RS1-441 |
| الوصف: | Background/Objectives: High fructose has been implicated as an important trigger of kidney inflammation in patients and experimental models. Magnolol, isolated from Magnolia officinalis, has an anti-inflammatory effect, but its protective role in podocytes remains underexplored. This study explored the protective effects and underlying mechanism of magnolol against high fructose-induced podocyte inflammation. Methods: The effects of magnolol on high fructose-induced podocyte inflammation were assessed in male Sprague Dawley rats administered 10% (w/v) fructose water for 12 weeks and heat-sensitive human podocyte cell lines (HPCs) exposed to 5 mM fructose. Podocyte foot processes were examined using transmission electron microscopy. The expression levels of nephrin, podocin, tumor necrosis factor-α (TNF-α), Notch1 intracellular domain (NICD1), triokinase/FMN cyclase (TKFC), specificity protein 1 (Sp1) and histone deacetylase 4 (HDAC4) were determined by Western blot, immunofluorescence and real-time quantitative polymerase chain reaction (qRT-PCR). The chromatin immunoprecipitation (ChIP) assay was performed to evaluate the interaction between Sp1 and the promoter region of HDAC4. Results: Magnolol mitigated the impairment of glomerular filtration function in high fructose-fed rats. Besides, it significantly alleviated the inflammatory responses in glomeruli and HPCs, evidenced by decreased protein levels of TNF-α and NICD1. Increased protein levels of TKFC, Sp1 and HDAC4 were observed in high fructose-stimulated HPCs and rat glomeruli. TMP195, an HDAC4 inhibitor, reduced TNF-α and NICD1 protein levels in high fructose-exposed HPCs. The increased Sp1 was shown to associate with the promoter region of HDAC4, promoting HDAC4 protein expression in high fructose-exposed HPCs. The knockdown of TKFC in HPCs by TKFC siRNA decreased Sp1, HDAC4 and NICD1 protein levels, alleviating podocyte inflammatory response. Furthermore, magnolol inhibited TKFC/Sp1/HDAC4/Notch1 activation in vivo and in vitro. Conclusions: Magnolol attenuated high fructose-induced podocyte inflammation possibly through the suppression of TKFC/Sp1/HDAC4/Notch1 activation, providing new evidence for its potential role in podocyte protection. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1424-8247 |
| Relation: | https://www.mdpi.com/1424-8247/17/11/1416; https://doaj.org/toc/1424-8247 |
| DOI: | 10.3390/ph17111416 |
| URL الوصول: | https://doaj.org/article/eaac0c24b6004d669c00a9349af97812 |
| رقم الانضمام: | edsdoj.0c24b6004d669c00a9349af97812 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14248247 |
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| DOI: | 10.3390/ph17111416 |