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miR-379-5p serves as a biomarker and regulates sepsis-associated acute kidney injury via targeting EDN1
Xiaoyu Wang1, Hongdong Li1, Xianfeng Yu2
1Department of Nephrology, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, Shandong Province, 255000, China.
Background:
Sepsis-associated acute kidney injury (SA-AKI) is a serious complication for sepsis patients, and microRNA (miRNA) is involved in its occurrence and development. This study investigated the clinical value of miR-379-5p and its potential mechanism on LPS-induced human proximal tubular epithelial cell lines (HK-2).
Methods:
Serum miR-379-5p levels were measured in 85 sepsis patients and 74 SA-AKI patients. The clinical significance of miR-379-5p was explored from the perspectives of SA-AKI diagnosis, kidney injury correlation, and 28-day survival assessment. The LPS-induced HK-2 cell model was constructed, and the regulatory effect of miR-379-5p on LPS-induced HK-2 cell viability and inflammatory response was analyzed. The regulatory mechanism was explored, focusing on the involvement of EDN1.
Results:
Low expression of serum miR-379-5p could distinguish SA-AKI from sepsis patients and was negatively correlated with serum creatinine (Scr), blood urea nitrogen (BUN), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), procalcitonin (PCT), and white blood cell (WBC). Low expression of miR-379-5p was correlated with the 28-day survival rate. LPS could inhibit the expression of miR-379-5p in HK-2 cells, inhibit cell viability, and promote the concentration of inflammatory factors TNF-α, IL-1β, and IL-6. Overexpression of miR-379-5p reversed the effect of LPS on HK-2 cells. EDN1 was a direct target gene of miR-379-5p. Overexpression of EDN1 counteracted the protective effect of miR-379-5p overexpression on HK-2 cells.
Conclusions:
Downregulated serum miR-379-5p had the potential value in diagnosing SA-AKI and forecasting 28-day patient survival. Overexpression of miR-379-5p protected HK-2 cells from LPS-induced injury by targeting and inhibiting EDN1.
Insights
Low serum miR-379-5p levels can help diagnose sepsis-associated acute kidney injury (SA-AKI) and predict patient survival. MiR-379-5p protects kidney cells from injury by targeting EDN1.
Area of Science:
- Biochemistry
- Molecular Biology
- Nephrology
Background:
- Sepsis-associated acute kidney injury (SA-AKI) is a critical complication in sepsis patients.
- MicroRNAs (miRNAs) play a role in the development of SA-AKI.
- Investigating specific miRNAs like miR-379-5p is crucial for understanding SA-AKI pathogenesis.
Purpose of the Study:
- To evaluate the clinical significance of serum miR-379-5p in diagnosing SA-AKI.
- To assess the correlation between miR-379-5p levels and kidney injury markers.
- To explore the protective mechanism of miR-379-5p in lipopolysaccharide (LPS)-induced kidney injury.
Main Methods:
- Serum miR-379-5p levels were quantified in sepsis and SA-AKI patients.
- Correlation analyses were performed between miR-379-5p and clinical parameters (Scr, BUN, Cys-C, KIM-1, CRP, PCT, WBC).
- An in vitro model using LPS-stimulated HK-2 cells was employed to study miR-379-5p's function and its interaction with EDN1.
Main Results:
- Lower serum miR-379-5p expression was observed in SA-AKI patients compared to sepsis patients.
- miR-379-5p levels negatively correlated with kidney injury markers and inflammatory indicators.
- Overexpression of miR-379-5p mitigated LPS-induced HK-2 cell damage and inflammation by targeting EDN1.
Conclusions:
- Downregulated serum miR-379-5p is a potential biomarker for SA-AKI diagnosis and predicting 28-day survival.
- miR-379-5p exerts a protective effect against LPS-induced kidney injury in HK-2 cells.
- The protective mechanism involves targeting and inhibiting the expression of EDN1.
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