Work

miRNA let-7a regulates apoptosis in renal tubular epithelial cells involved in sepsis-associated acute kidney injury

Year: 2025

Type: article

Abstract: OBJECTIVE: To investigate the molecular mechanism by which the miRNA let-7a regulates renal tubular epithelial cell apoptosis by influencing the activity of the PI3K/Akt pathway, which is involved in the development of sepsis-associated acute kidney injury (SA-AKI). METHODS: A sepsis-associated acute kidney injury model was constructed in vitro and in vivo using LPS, and the expression of the miRNA let-7a and activation of the PI3K/Akt pathway were detected in SA-AKI. Apoptosis marker molecules and inflammatory factor expression were detected by transfecting miRNA let-7a mimics with LPS-stimulated human renal tubular epithelial cells (HKCs) or using the PI3K/Akt pathway inhibitor LY294002. Bioassay analysis elucidated the relationship between miRNA let-7a and the PI3K/Akt signaling pathway. The mechanism was validated in primary renal tubular epithelial cells. RESULTS: In the in vivo and in vitro models, miRNA let-7a expression was significantly reduced, and the PI3K/Akt pathway was activated. When miRNA let-7a was overexpressed or the PI3K/Akt pathway was inhibited, the inflammatory response of renal tubular epithelial cells was attenuated. Bioassay analysis verified that the miRNA let-7a binds to the PI3K/Akt signaling pathway. The miRNA let-7a-PI3K/Akt regulatory axis regulates the apoptosis of renal tubular epithelial cells in primary tubular epithelial cells. CONCLUSION: The miRNA let-7a regulates inflammation and apoptosis in renal tubular epithelial cells by affecting the activity of the PI3K/Akt pathway in the development of sepsis-associated acute kidney injury.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2025.114485