miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis

Abstract

Sepsis-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.

Keywords:

• microRNAs
• miR-16-5p
• apoptosis
• sepsis-associated acute kidney injury
• potential biomarker

Acknowledgments

Not applicable.

Authors’ contributions

Han Li, Junyan Duan: Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the article.

Tongtong Zhang, Yingjie Fu, Yue Xu: Contributed reagents, materials, analysis tools or data; Analyzed and interpreted the data.

Xuhua Ge and Hongjun Miao: Conceived and designed the experiments.

Ethics approval and consent to participate

This animal study was approved by the Experimental Animal Ethics Committee of Nanjing Medical University (approval number: 20210229), all methods were carried out in accordance with relevant guidelines and regulations. This study was carried out in compliance with the ARRIVE guidelines.

The clinical study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Ethics Committee of the Children’s Hospital of Nanjing Medical University (approval number: 202008056-1), and informed consent was obtained from all parents of the children.

Consent for publication

All authors approved the final manuscript and the submission to this journal.

Disclosure statement

The authors have no conflicts of interest to declare.

Availability of data and materials

The original contributions presented in the study are included in the article, and further inquiries can be directed to the corresponding authors.

Additional information

Funding

This research was supported by the National Natural Science Foundation of China (No.: 82170733) and Nanjing Medical University Science and Technology Development Fund (No.: NMUB20220019).