A potential link between fibroblast growth factor-23 and the progression of AKI to CKD
Abstract Background Patients who recover from acute kidney injury (AKI) have a 25% increase in the risk of chronic kidney disease (CKD) and a 50% increase in mortality after a follow-up of approximately 10 years. Circulating FGF-23 increases significantly early in the development of AKI, is signific...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | BMC Nephrology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12882-023-03125-1 |
| _version_ | 1797850183206174720 |
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| author | Yinghui Lu Shutian Xu Rong Tang Cui Han Chunxia Zheng |
| author_facet | Yinghui Lu Shutian Xu Rong Tang Cui Han Chunxia Zheng |
| author_sort | Yinghui Lu |
| collection | DOAJ |
| description | Abstract Background Patients who recover from acute kidney injury (AKI) have a 25% increase in the risk of chronic kidney disease (CKD) and a 50% increase in mortality after a follow-up of approximately 10 years. Circulating FGF-23 increases significantly early in the development of AKI, is significantly elevated in patients with CKD and has become a major biomarker of poor clinical prognosis in CKD. However, the potential link between fibroblast growth factor-23 levels and the progression of AKI to CKD remains unclear. Method Serum FGF-23 levels in AKI patients and ischaemia‒reperfusion injury (IRI) mice were detected with ELISA. Cultured HK2 cells were incubated with FGF-23 and PD173074, a blocker of FGFR, and then TGFβ/Smad and Wnt/β-catenin were examined with immunofluorescence and immunoblotting. Quantitative real-time polymerase chain reaction was used to detect the expression of COL1A1 and COL4A1. Histologic staining confirmed renal fibrosis. Results The level of serum FGF-23 was significantly different between AKI patients and healthy controls (P < 0.01). Moreover, serum FGF-23 levels in the CKD progression group were significantly higher than those in the non-CKD progression group of AKI patients (P < 0.01). In the AKI-CKD mouse model, serum FGF-23 levels were increased, and renal fibrosis occurred; moreover, the protein expression of β-catenin and p-Smad3 was upregulated. PD173074 downregulated the expression of β-catenin and p-Smad3 and reduced fibrosis in both mice and HK2 cells. Conclusion The increase in FGF-23 may be associated with the progression of AKI to CKD and may mediate renal fibrosis via TGF-β and Wnt/β-catenin activation. |
| first_indexed | 2024-04-09T18:56:18Z |
| format | Article |
| id | doaj.art-af6f0d39ea124d40bc6144edf361562a |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-04-09T18:56:18Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-af6f0d39ea124d40bc6144edf361562a2023-04-09T11:10:31ZengBMCBMC Nephrology1471-23692023-04-012411710.1186/s12882-023-03125-1A potential link between fibroblast growth factor-23 and the progression of AKI to CKDYinghui Lu0Shutian Xu1Rong Tang2Cui Han3Chunxia Zheng4Jinling Hospital, National Clinical Research Center of Kidney Diseases, Nanjing University School of MedicineJinling Hospital, National Clinical Research Center of Kidney Diseases, Nanjing University School of MedicineJinling Hospital, National Clinical Research Center of Kidney Diseases, Nanjing University School of MedicineJinling Hospital, National Clinical Research Center of Kidney Diseases, Nanjing University School of MedicineJinling Hospital, National Clinical Research Center of Kidney Diseases, Nanjing University School of MedicineAbstract Background Patients who recover from acute kidney injury (AKI) have a 25% increase in the risk of chronic kidney disease (CKD) and a 50% increase in mortality after a follow-up of approximately 10 years. Circulating FGF-23 increases significantly early in the development of AKI, is significantly elevated in patients with CKD and has become a major biomarker of poor clinical prognosis in CKD. However, the potential link between fibroblast growth factor-23 levels and the progression of AKI to CKD remains unclear. Method Serum FGF-23 levels in AKI patients and ischaemia‒reperfusion injury (IRI) mice were detected with ELISA. Cultured HK2 cells were incubated with FGF-23 and PD173074, a blocker of FGFR, and then TGFβ/Smad and Wnt/β-catenin were examined with immunofluorescence and immunoblotting. Quantitative real-time polymerase chain reaction was used to detect the expression of COL1A1 and COL4A1. Histologic staining confirmed renal fibrosis. Results The level of serum FGF-23 was significantly different between AKI patients and healthy controls (P < 0.01). Moreover, serum FGF-23 levels in the CKD progression group were significantly higher than those in the non-CKD progression group of AKI patients (P < 0.01). In the AKI-CKD mouse model, serum FGF-23 levels were increased, and renal fibrosis occurred; moreover, the protein expression of β-catenin and p-Smad3 was upregulated. PD173074 downregulated the expression of β-catenin and p-Smad3 and reduced fibrosis in both mice and HK2 cells. Conclusion The increase in FGF-23 may be associated with the progression of AKI to CKD and may mediate renal fibrosis via TGF-β and Wnt/β-catenin activation.https://doi.org/10.1186/s12882-023-03125-1AKI – CKDRenal fibrosisFGF-23 |
| spellingShingle | Yinghui Lu Shutian Xu Rong Tang Cui Han Chunxia Zheng A potential link between fibroblast growth factor-23 and the progression of AKI to CKD BMC Nephrology AKI – CKD Renal fibrosis FGF-23 |
| title | A potential link between fibroblast growth factor-23 and the progression of AKI to CKD |
| title_full | A potential link between fibroblast growth factor-23 and the progression of AKI to CKD |
| title_fullStr | A potential link between fibroblast growth factor-23 and the progression of AKI to CKD |
| title_full_unstemmed | A potential link between fibroblast growth factor-23 and the progression of AKI to CKD |
| title_short | A potential link between fibroblast growth factor-23 and the progression of AKI to CKD |
| title_sort | potential link between fibroblast growth factor 23 and the progression of aki to ckd |
| topic | AKI – CKD Renal fibrosis FGF-23 |
| url | https://doi.org/10.1186/s12882-023-03125-1 |
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