Work

LncRNA AK154753 mediates the development of acute kidney ischemia reperfusion injury via the miR-345-3p/Bak and miR-708-5p/Bim pathways.

Year: 2025

Type: article

Abstract: OBJECTIVES: Acute kidney injury (AKI) is a clinical syndrome characterized by sudden deterioration of renal function, with ischemia reperfusion injury (IRI) being the most common cause. Long noncoding RNA (lncRNA) regulate cell fate through interactions with microRNA (miRNA) and messenger RNAs (mRNA), but the mechanisms and regulatory networks underlying lncRNA AK154753 (AK154753) in IRI-induced AKI remain unclear. This study aims to investigate the role of AK154753 in acute renal IRI and to elucidate the molecular mechanism of the AK154753 via miR-345-3p/Bcl-2 homologous antagonist/killer (Bak) and miR-708-5p/Bcl-2 interacting mediator of cell death (Bim) axis. METHODS: A bilateral renal artery ischemia model was established in mice (30 minutes ischemia followed by 24 hours and 48 hours reperfusion). Kidney tissues were analyzed using microarray-based transcriptomic sequencing to identify differentially expressed lncRNAs, miRNAs, and mRNAs. RNA levels of AK154753, miR-345-3p, miR-708-5p, Bak, and Bim were validated using real-time reverse transcription PCR (real-time RT-PCR). Oxygen and glucose deprivation/reperfusion (OGD/R) models were constructed in mouse proximal renal tubular epithelial BUMPT cells to simulate in vitro IRI conditions. Adeno-associated virus (AAV)-mediated shRNA was used to silence AK154753 in vivo. Apoptosis was assessed using TUNEL staining and flow cytometry. Protein levels of Bak, Bim, and cleaved-caspase-3 were measured using Western blotting. Fluorescence in situ hybridization (FISH) was used to determine intracellular localization of AK154753. Binding relationships between AK154753 and miR-345-3p/Bak and miR-708-5p/Bim were verified using dual-luciferase reporter assays. MiRNA mimics and inhibitors were used to evaluate regulatory-network integrity. RESULTS: <0.01). CONCLUSIONS: AK154753 is upregulated in acute renal IRI and promotes apoptosis by suppressing miR-345-3p and miR-708-5p, thereby upregulating Bak and Bim, and participates in the initiation and progression of acute renal IRI.

Source: PubMed

DOI: 10.11817/j.issn.1672-7347.2025.240687