FGF21 ameliorates diabetic nephropathy through CDK1-dependently regulating the cell cycle
BackgroundDiabetic nephropathy (DN) is a prevalent global renal illness and one of the main causes of end-stage renal disease (ESRD). FGF21 has been shown to ameliorate diabetic nephropathy, and in addition FGF-21-treated mice impeded mitogenicity, whereas it is unclear whether FGF21 can influence D...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1500458/full |
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| author | Yudie Zhang Yudie Zhang Yudie Zhang Yudie Zhang Yudie Zhang Fan Wang Fan Wang Fan Wang Fan Wang Chongyang Zhang Chongyang Zhang Chongyang Zhang Chongyang Zhang Fan Yao Fan Yao Fan Yao Fan Yao Bin Zhang Bin Zhang Bin Zhang Bin Zhang Yongping Zhang Xiaobo Sun Xiaobo Sun Xiaobo Sun Xiaobo Sun |
| author_facet | Yudie Zhang Yudie Zhang Yudie Zhang Yudie Zhang Yudie Zhang Fan Wang Fan Wang Fan Wang Fan Wang Chongyang Zhang Chongyang Zhang Chongyang Zhang Chongyang Zhang Fan Yao Fan Yao Fan Yao Fan Yao Bin Zhang Bin Zhang Bin Zhang Bin Zhang Yongping Zhang Xiaobo Sun Xiaobo Sun Xiaobo Sun Xiaobo Sun |
| author_sort | Yudie Zhang |
| collection | DOAJ |
| description | BackgroundDiabetic nephropathy (DN) is a prevalent global renal illness and one of the main causes of end-stage renal disease (ESRD). FGF21 has been shown to ameliorate diabetic nephropathy, and in addition FGF-21-treated mice impeded mitogenicity, whereas it is unclear whether FGF21 can influence DN progression by regulating the cell cycle in diabetic nephropathy.MethodsIn order to create a diabetic model, STZ injections were given to C57BL/6J mice for this investigation. Then, FGF21 was administered, and renal tissue examination and pathological observation were combined with an assessment of glomerular injury, inflammation, oxidative stress, and the fibrinogen system in mice following the administration of the intervention. Furthermore, we used db/db mice and FGF21 direct therapy for 8 weeks to investigate changes in fasting glucose and creatinine expression as well as pathological changes in glomeruli glycogen deposition, fibrosis, and nephrin expression. To investigate the mechanism of action of FGF21 in the treatment of glycolytic kidney, transcriptome sequencing of renal tissues and KEGG pathway enrichment analysis of differential genes were performed.ResultsThe study’s findings demonstrated that FGF21 intervention increased clotting time, decreased oxidative stress and inflammation, and avoided thrombosis in addition to considerably improving glomerular filtration damage. After 8 weeks of FGF21 treatment, glomerular glycogen deposition, fibrosis, and renin expression decreased in db/db mice. Moreover, there was a notable reduction of creatinine and fasting blood glucose levels. Additionally, the CDK1 gene, a key player in controlling the cell cycle, was discovered through examination of the transcriptome sequencing data. It was also shown that FGF21 dramatically reduces the expression of CDK1, which may help diabetic nephropathy by averting mitotic catastrophe and changing the renal cell cycle.ConclusionIn short, FGF21 improved the development of diabetic nephropathy in diabetic nephropathy-affected animals by reducing glomerular filtration damage, inflammation, and oxidative stress, inhibiting the formation of thrombus, and controlling the cell cycle through CDK1. |
| format | Article |
| id | doaj-art-47bb5a25868d42ed89d7fd4409ee8028 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-47bb5a25868d42ed89d7fd4409ee80282025-01-03T06:47:24ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15004581500458FGF21 ameliorates diabetic nephropathy through CDK1-dependently regulating the cell cycleYudie Zhang0Yudie Zhang1Yudie Zhang2Yudie Zhang3Yudie Zhang4Fan Wang5Fan Wang6Fan Wang7Fan Wang8Chongyang Zhang9Chongyang Zhang10Chongyang Zhang11Chongyang Zhang12Fan Yao13Fan Yao14Fan Yao15Fan Yao16Bin Zhang17Bin Zhang18Bin Zhang19Bin Zhang20Yongping Zhang21Xiaobo Sun22Xiaobo Sun23Xiaobo Sun24Xiaobo Sun25Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaInstitute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, ChinaKey Laboratory of efficacy evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing, ChinaInstitute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, ChinaKey Laboratory of efficacy evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing, ChinaInstitute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, ChinaKey Laboratory of efficacy evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing, ChinaInstitute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, ChinaKey Laboratory of efficacy evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing, ChinaInstitute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, ChinaKey Laboratory of efficacy evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing, ChinaGuizhou University of Traditional Chinese Medicine, Guiyang, ChinaInstitute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, ChinaKey Laboratory of efficacy evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing, ChinaBackgroundDiabetic nephropathy (DN) is a prevalent global renal illness and one of the main causes of end-stage renal disease (ESRD). FGF21 has been shown to ameliorate diabetic nephropathy, and in addition FGF-21-treated mice impeded mitogenicity, whereas it is unclear whether FGF21 can influence DN progression by regulating the cell cycle in diabetic nephropathy.MethodsIn order to create a diabetic model, STZ injections were given to C57BL/6J mice for this investigation. Then, FGF21 was administered, and renal tissue examination and pathological observation were combined with an assessment of glomerular injury, inflammation, oxidative stress, and the fibrinogen system in mice following the administration of the intervention. Furthermore, we used db/db mice and FGF21 direct therapy for 8 weeks to investigate changes in fasting glucose and creatinine expression as well as pathological changes in glomeruli glycogen deposition, fibrosis, and nephrin expression. To investigate the mechanism of action of FGF21 in the treatment of glycolytic kidney, transcriptome sequencing of renal tissues and KEGG pathway enrichment analysis of differential genes were performed.ResultsThe study’s findings demonstrated that FGF21 intervention increased clotting time, decreased oxidative stress and inflammation, and avoided thrombosis in addition to considerably improving glomerular filtration damage. After 8 weeks of FGF21 treatment, glomerular glycogen deposition, fibrosis, and renin expression decreased in db/db mice. Moreover, there was a notable reduction of creatinine and fasting blood glucose levels. Additionally, the CDK1 gene, a key player in controlling the cell cycle, was discovered through examination of the transcriptome sequencing data. It was also shown that FGF21 dramatically reduces the expression of CDK1, which may help diabetic nephropathy by averting mitotic catastrophe and changing the renal cell cycle.ConclusionIn short, FGF21 improved the development of diabetic nephropathy in diabetic nephropathy-affected animals by reducing glomerular filtration damage, inflammation, and oxidative stress, inhibiting the formation of thrombus, and controlling the cell cycle through CDK1.https://www.frontiersin.org/articles/10.3389/fphar.2024.1500458/fullFGF21diabetic nephropathyCDK1cell cycleglomerular filtration barrier |
| spellingShingle | Yudie Zhang Yudie Zhang Yudie Zhang Yudie Zhang Yudie Zhang Fan Wang Fan Wang Fan Wang Fan Wang Chongyang Zhang Chongyang Zhang Chongyang Zhang Chongyang Zhang Fan Yao Fan Yao Fan Yao Fan Yao Bin Zhang Bin Zhang Bin Zhang Bin Zhang Yongping Zhang Xiaobo Sun Xiaobo Sun Xiaobo Sun Xiaobo Sun FGF21 ameliorates diabetic nephropathy through CDK1-dependently regulating the cell cycle Frontiers in Pharmacology FGF21 diabetic nephropathy CDK1 cell cycle glomerular filtration barrier |
| title | FGF21 ameliorates diabetic nephropathy through CDK1-dependently regulating the cell cycle |
| title_full | FGF21 ameliorates diabetic nephropathy through CDK1-dependently regulating the cell cycle |
| title_fullStr | FGF21 ameliorates diabetic nephropathy through CDK1-dependently regulating the cell cycle |
| title_full_unstemmed | FGF21 ameliorates diabetic nephropathy through CDK1-dependently regulating the cell cycle |
| title_short | FGF21 ameliorates diabetic nephropathy through CDK1-dependently regulating the cell cycle |
| title_sort | fgf21 ameliorates diabetic nephropathy through cdk1 dependently regulating the cell cycle |
| topic | FGF21 diabetic nephropathy CDK1 cell cycle glomerular filtration barrier |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1500458/full |
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