Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway
Aims Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD ren...
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| Main Authors: | , , , , , , , , |
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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.2024.2371988 |
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| author | Xiao-ying Yang Die Jiang Yuan-zhu Wang Mei-yan Duan Ye-wei Huang Xuan-jun Wang Ze-min Xiang Jun Sheng Qiang-qiang Zhu |
| author_facet | Xiao-ying Yang Die Jiang Yuan-zhu Wang Mei-yan Duan Ye-wei Huang Xuan-jun Wang Ze-min Xiang Jun Sheng Qiang-qiang Zhu |
| author_sort | Xiao-ying Yang |
| collection | DOAJ |
| description | Aims Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis.Methods This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein.Results In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was −6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1.Conclusion CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways. |
| format | Article |
| id | doaj-art-174e77b75fcf4bc683b8193f710bcf78 |
| 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-174e77b75fcf4bc683b8193f710bcf782025-08-20T02:38:10ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2371988Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathwayXiao-ying Yang0Die Jiang1Yuan-zhu Wang2Mei-yan Duan3Ye-wei Huang4Xuan-jun Wang5Ze-min Xiang6Jun Sheng7Qiang-qiang Zhu8Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaAims Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis.Methods This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein.Results In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was −6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1.Conclusion CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2371988Chlorogenic aciddiabetic kidney diseaserenal fibrosisrenal lipid accumulationNotch1Stat3 |
| spellingShingle | Xiao-ying Yang Die Jiang Yuan-zhu Wang Mei-yan Duan Ye-wei Huang Xuan-jun Wang Ze-min Xiang Jun Sheng Qiang-qiang Zhu Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway Renal Failure Chlorogenic acid diabetic kidney disease renal fibrosis renal lipid accumulation Notch1 Stat3 |
| title | Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway |
| title_full | Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway |
| title_fullStr | Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway |
| title_full_unstemmed | Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway |
| title_short | Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway |
| title_sort | chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the notch1 and stat3 signaling pathway |
| topic | Chlorogenic acid diabetic kidney disease renal fibrosis renal lipid accumulation Notch1 Stat3 |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2371988 |
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