Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism
Abstract Background The anti-aging protein Klotho plays a protective role in kidney disease, but its potential as a biomarker for chronic kidney disease (CKD) is controversial. Additionally, the main pathways through which Klotho exerts its effects on CKD remain unclear. Therefore, we used bioinform...
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-024-01226-4 |
| _version_ | 1797209035045339136 |
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| author | Junhui Liu Huaicheng Wang Qinyu Liu Shushu Long Yanfang Wu Nengying Wang Wei Lin Gang Chen Miao Lin Junping Wen |
| author_facet | Junhui Liu Huaicheng Wang Qinyu Liu Shushu Long Yanfang Wu Nengying Wang Wei Lin Gang Chen Miao Lin Junping Wen |
| author_sort | Junhui Liu |
| collection | DOAJ |
| description | Abstract Background The anti-aging protein Klotho plays a protective role in kidney disease, but its potential as a biomarker for chronic kidney disease (CKD) is controversial. Additionally, the main pathways through which Klotho exerts its effects on CKD remain unclear. Therefore, we used bioinformatics and clinical data analysis to determine its role in CKD. Results We analyzed the transcriptomic and clinical data from the Nephroseq v5 database and found that the Klotho gene was mainly expressed in the tubulointerstitium, and its expression was significantly positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with blood urea nitrogen (BUN) in CKD. We further found that Klotho gene expression was mainly negatively associated with inflammatory response and positively associated with lipid metabolism in CKD tubulointerstitium by analyzing two large sample-size CKD tubulointerstitial transcriptome datasets. By analyzing 10-year clinical data from the National Health and Nutrition Examination Survey (NHANES) 2007–2016, we also found that Klotho negatively correlated with inflammatory biomarkers and triglyceride and positively correlated with eGFR in the CKD population. Mediation analysis showed that Klotho could improve renal function in the general population by modulating the inflammatory response and lipid metabolism, while in the CKD population, it primarily manifested by mediating the inflammatory response. Restricted cubic spline (RCS) analysis showed that the optimal concentration range for Klotho to exert its biological function was around 1000 pg/ml. Kaplan–Meier curves showed that lower cumulative hazards of all-cause mortality in participants with higher levels of Klotho. We also demonstrated that Klotho could reduce cellular inflammatory response and improve cellular lipid metabolism by establishing an in vitro model similar to CKD. Conclusions Our results suggest that Klotho exerts protection in CKD, which may be mainly related to the regulation of inflammatory response and lipid metabolism, and it can serve as a potential biomarker for CKD. |
| first_indexed | 2024-04-24T09:48:17Z |
| format | Article |
| id | doaj.art-02dbbc0cc28244529c988bf0292c1690 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-04-24T09:48:17Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-02dbbc0cc28244529c988bf0292c16902024-04-14T11:30:34ZengBMCCell & Bioscience2045-37012024-04-0114112910.1186/s13578-024-01226-4Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolismJunhui Liu0Huaicheng Wang1Qinyu Liu2Shushu Long3Yanfang Wu4Nengying Wang5Wei Lin6Gang Chen7Miao Lin8Junping Wen9Shengli Clinical Medical College of Fujian Medical University, Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical University, Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical University, Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical University, Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical University, Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical University, Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical University, Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical University, Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical University, Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical University, Fujian Medical UniversityAbstract Background The anti-aging protein Klotho plays a protective role in kidney disease, but its potential as a biomarker for chronic kidney disease (CKD) is controversial. Additionally, the main pathways through which Klotho exerts its effects on CKD remain unclear. Therefore, we used bioinformatics and clinical data analysis to determine its role in CKD. Results We analyzed the transcriptomic and clinical data from the Nephroseq v5 database and found that the Klotho gene was mainly expressed in the tubulointerstitium, and its expression was significantly positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with blood urea nitrogen (BUN) in CKD. We further found that Klotho gene expression was mainly negatively associated with inflammatory response and positively associated with lipid metabolism in CKD tubulointerstitium by analyzing two large sample-size CKD tubulointerstitial transcriptome datasets. By analyzing 10-year clinical data from the National Health and Nutrition Examination Survey (NHANES) 2007–2016, we also found that Klotho negatively correlated with inflammatory biomarkers and triglyceride and positively correlated with eGFR in the CKD population. Mediation analysis showed that Klotho could improve renal function in the general population by modulating the inflammatory response and lipid metabolism, while in the CKD population, it primarily manifested by mediating the inflammatory response. Restricted cubic spline (RCS) analysis showed that the optimal concentration range for Klotho to exert its biological function was around 1000 pg/ml. Kaplan–Meier curves showed that lower cumulative hazards of all-cause mortality in participants with higher levels of Klotho. We also demonstrated that Klotho could reduce cellular inflammatory response and improve cellular lipid metabolism by establishing an in vitro model similar to CKD. Conclusions Our results suggest that Klotho exerts protection in CKD, which may be mainly related to the regulation of inflammatory response and lipid metabolism, and it can serve as a potential biomarker for CKD.https://doi.org/10.1186/s13578-024-01226-4KlothoChronic kidney diseaseInflammatory responseLipid metabolismBiomarker |
| spellingShingle | Junhui Liu Huaicheng Wang Qinyu Liu Shushu Long Yanfang Wu Nengying Wang Wei Lin Gang Chen Miao Lin Junping Wen Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism Cell & Bioscience Klotho Chronic kidney disease Inflammatory response Lipid metabolism Biomarker |
| title | Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism |
| title_full | Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism |
| title_fullStr | Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism |
| title_full_unstemmed | Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism |
| title_short | Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism |
| title_sort | klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism |
| topic | Klotho Chronic kidney disease Inflammatory response Lipid metabolism Biomarker |
| url | https://doi.org/10.1186/s13578-024-01226-4 |
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