Recombinant α-Klotho Protein Alleviated Acute Cardiorenal Injury in a Mouse Model of Lipopolysaccharide-Induced Septic Cardiorenal Syndrome Type 5
Background and Aims. Klotho is an aging-suppressor gene mainly expressed in the renal tubules. The klotho gene encodes the α-klotho protein, which has many functions. Previous studies have found that α-klotho protein has a cardiorenal protective function. α-Klotho deficiency renders the kidney more...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2019/5853426 |
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| author | Xi Liu Yangyang Niu Xiaoqin Zhang Yingying Zhang Ying Yu Jieli Huang Jiangtao Li Chen Yu |
| author_facet | Xi Liu Yangyang Niu Xiaoqin Zhang Yingying Zhang Ying Yu Jieli Huang Jiangtao Li Chen Yu |
| author_sort | Xi Liu |
| collection | DOAJ |
| description | Background and Aims. Klotho is an aging-suppressor gene mainly expressed in the renal tubules. The klotho gene encodes the α-klotho protein, which has many functions. Previous studies have found that α-klotho protein has a cardiorenal protective function. α-Klotho deficiency renders the kidney more susceptible to injury and results in cardiovascular calcification and left ventricular hypertrophy in chronic kidney disease. However, the role of α-klotho in acute heart injury and acute kidney injury with sepsis remains unknown. This study aimed to investigate the effects and mechanisms of α-klotho in septic cardiorenal injury. Methods. Male 8-week-old C57BL/6 mice were randomly assigned to the control group, lipopolysaccharide (LPS; 10 mg/kg) group, LPS (10 mg/kg)+α-klotho (0.01 mg/kg) group, and LPS (10 mg/kg)+α-klotho (0.02 mg/kg) group. Recombinant α-klotho was intraperitoneally injected an hour before LPS injection. Mice were euthanized at 24 h after LPS injection. The serum troponin, brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), and creatinine levels were measured in all groups at 24 h. Biomarkers of mice heart apoptosis, inflammation, oxidative stress, and endoplasmic reticulum stress, such as caspase-3, interleukin 1 (IL-1), reactive oxygen species (ROS), and glucose-regulated protein 78 (GRP78), were also measured. Results. α-Klotho was mainly expressed in mice kidneys and was undetectable in the control mice hearts. α-Klotho substantially decreased after LPS injection. In the LPS group, the serum troponin levels significantly increased as early as 6 h (p<0.05) after LPS injection, while the BNP, NGAL, and creatinine levels significantly increased at 24 h (p<0.05). Pretreatment with α-klotho significantly ameliorated acute cardiorenal injury. In the LPS+α-klotho (0.01 mg/kg) group, the levels of apoptosis, inflammation, and oxidative stress were decreased, while the level of endoplasmic reticulum stress was elevated. Conclusions. α-Klotho significantly alleviates acute cardiorenal injury in LPS-induced septic cardiorenal injury due to the inhibition of apoptosis, inflammation, and oxidation, as well as the regulation of endoplasmic reticulum stress levels. |
| format | Article |
| id | doaj-art-99713bdc5a2b4c9988a6cceca3d83c00 |
| institution | Kabale University |
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| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
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| series | Analytical Cellular Pathology |
| spelling | doaj-art-99713bdc5a2b4c9988a6cceca3d83c002025-02-03T06:00:23ZengWileyAnalytical Cellular Pathology2210-71772210-71852019-01-01201910.1155/2019/58534265853426Recombinant α-Klotho Protein Alleviated Acute Cardiorenal Injury in a Mouse Model of Lipopolysaccharide-Induced Septic Cardiorenal Syndrome Type 5Xi Liu0Yangyang Niu1Xiaoqin Zhang2Yingying Zhang3Ying Yu4Jieli Huang5Jiangtao Li6Chen Yu7The Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaThe Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaThe Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaThe Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaThe Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaThe Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaThe Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaThe Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaBackground and Aims. Klotho is an aging-suppressor gene mainly expressed in the renal tubules. The klotho gene encodes the α-klotho protein, which has many functions. Previous studies have found that α-klotho protein has a cardiorenal protective function. α-Klotho deficiency renders the kidney more susceptible to injury and results in cardiovascular calcification and left ventricular hypertrophy in chronic kidney disease. However, the role of α-klotho in acute heart injury and acute kidney injury with sepsis remains unknown. This study aimed to investigate the effects and mechanisms of α-klotho in septic cardiorenal injury. Methods. Male 8-week-old C57BL/6 mice were randomly assigned to the control group, lipopolysaccharide (LPS; 10 mg/kg) group, LPS (10 mg/kg)+α-klotho (0.01 mg/kg) group, and LPS (10 mg/kg)+α-klotho (0.02 mg/kg) group. Recombinant α-klotho was intraperitoneally injected an hour before LPS injection. Mice were euthanized at 24 h after LPS injection. The serum troponin, brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), and creatinine levels were measured in all groups at 24 h. Biomarkers of mice heart apoptosis, inflammation, oxidative stress, and endoplasmic reticulum stress, such as caspase-3, interleukin 1 (IL-1), reactive oxygen species (ROS), and glucose-regulated protein 78 (GRP78), were also measured. Results. α-Klotho was mainly expressed in mice kidneys and was undetectable in the control mice hearts. α-Klotho substantially decreased after LPS injection. In the LPS group, the serum troponin levels significantly increased as early as 6 h (p<0.05) after LPS injection, while the BNP, NGAL, and creatinine levels significantly increased at 24 h (p<0.05). Pretreatment with α-klotho significantly ameliorated acute cardiorenal injury. In the LPS+α-klotho (0.01 mg/kg) group, the levels of apoptosis, inflammation, and oxidative stress were decreased, while the level of endoplasmic reticulum stress was elevated. Conclusions. α-Klotho significantly alleviates acute cardiorenal injury in LPS-induced septic cardiorenal injury due to the inhibition of apoptosis, inflammation, and oxidation, as well as the regulation of endoplasmic reticulum stress levels.http://dx.doi.org/10.1155/2019/5853426 |
| spellingShingle | Xi Liu Yangyang Niu Xiaoqin Zhang Yingying Zhang Ying Yu Jieli Huang Jiangtao Li Chen Yu Recombinant α-Klotho Protein Alleviated Acute Cardiorenal Injury in a Mouse Model of Lipopolysaccharide-Induced Septic Cardiorenal Syndrome Type 5 Analytical Cellular Pathology |
| title | Recombinant α-Klotho Protein Alleviated Acute Cardiorenal Injury in a Mouse Model of Lipopolysaccharide-Induced Septic Cardiorenal Syndrome Type 5 |
| title_full | Recombinant α-Klotho Protein Alleviated Acute Cardiorenal Injury in a Mouse Model of Lipopolysaccharide-Induced Septic Cardiorenal Syndrome Type 5 |
| title_fullStr | Recombinant α-Klotho Protein Alleviated Acute Cardiorenal Injury in a Mouse Model of Lipopolysaccharide-Induced Septic Cardiorenal Syndrome Type 5 |
| title_full_unstemmed | Recombinant α-Klotho Protein Alleviated Acute Cardiorenal Injury in a Mouse Model of Lipopolysaccharide-Induced Septic Cardiorenal Syndrome Type 5 |
| title_short | Recombinant α-Klotho Protein Alleviated Acute Cardiorenal Injury in a Mouse Model of Lipopolysaccharide-Induced Septic Cardiorenal Syndrome Type 5 |
| title_sort | recombinant α klotho protein alleviated acute cardiorenal injury in a mouse model of lipopolysaccharide induced septic cardiorenal syndrome type 5 |
| url | http://dx.doi.org/10.1155/2019/5853426 |
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