miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis
AbstractSepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers...
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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.2024.2322688 |
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author | Han Li Junyan Duan Tongtong Zhang Yingjie Fu Yue Xu Hongjun Miao Xuhua Ge |
author_facet | Han Li Junyan Duan Tongtong Zhang Yingjie Fu Yue Xu Hongjun Miao Xuhua Ge |
author_sort | Han Li |
collection | DOAJ |
description | AbstractSepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). In vitro, the expression level of miR-16-5p in HK-2 cells treated with 10 μg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1β, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI. |
first_indexed | 2024-03-07T14:20:10Z |
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institution | Directory Open Access Journal |
issn | 0886-022X 1525-6049 |
language | English |
last_indexed | 2024-03-07T14:20:10Z |
publishDate | 2024-12-01 |
publisher | Taylor & Francis Group |
record_format | Article |
series | Renal Failure |
spelling | doaj.art-28cdb6e65b1a42e394eeca420b24bb662024-03-06T09:16:32ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2322688miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosisHan Li0Junyan Duan1Tongtong Zhang2Yingjie Fu3Yue Xu4Hongjun Miao5Xuhua Ge6Department of Emergency/Critical Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, PR ChinaDepartment of Pediatrics, Changzhou Second Peoples Hospital Affiliated to Nanjing Medical University, Changzhou, PR ChinaDepartment of Emergency/Critical Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, PR ChinaDepartment of Emergency/Critical Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, PR ChinaDepartment of Emergency/Critical Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, PR ChinaDepartment of Emergency/Critical Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, PR ChinaDepartment of Emergency/Critical Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, PR ChinaAbstractSepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). In vitro, the expression level of miR-16-5p in HK-2 cells treated with 10 μg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1β, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2322688microRNAsmiR-16-5papoptosissepsis-associated acute kidney injurypotential biomarker |
spellingShingle | Han Li Junyan Duan Tongtong Zhang Yingjie Fu Yue Xu Hongjun Miao Xuhua Ge miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis Renal Failure microRNAs miR-16-5p apoptosis sepsis-associated acute kidney injury potential biomarker |
title | miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis |
title_full | miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis |
title_fullStr | miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis |
title_full_unstemmed | miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis |
title_short | miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis |
title_sort | mir 16 5p aggravates sepsis associated acute kidney injury by inducing apoptosis |
topic | microRNAs miR-16-5p apoptosis sepsis-associated acute kidney injury potential biomarker |
url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2322688 |
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