MicroRNA-34b-5p Modulates Sepsis-Induced Acute Kidney Injury via the LMX1B/HIGD1A Axis: Implications for Molecular Therapeutics.
Year: 2026
Type: article
Abstract: Background: Sepsis-induced acute kidney injury (AKI) represents a critical complication with high mortality, largely due to the absence of specific targeted treatments MicroRNAs (miRNAs) are emerging as critical regulators in AKI pathogenesis, but their specific molecular mechanisms and biotechnological applications remain unclear. Objectives: This research sought to clarify the functional significance of miR-34b-5p and its regulatory mechanism involving the LMX1B/HIGD1A signaling axis in sepsis-induced acute kidney injury (AKI), while also investigating its potential as a novel biotechnological therapeutic target. Materials and Methods: We established in vitro (LPS-stimulated HK-2 human renal tubular cells) and in vivo (murine cecal ligation and puncture, CLP) models of sepsis-induced AKI. An integrated strategy was employed, combining functional analysis, gene and protein expression detection, as well as the exploration of intermolecular interaction mechanisms, to deeply dissect the operational mechanism of the miR-34b-5p/LMX1B/HIGD1A regulatory axis. Results: In acute kidney injury caused by sepsis, the expression level of miR-34b-5p significantly increases, which further leads to the reduction of LMX1B and HIGD1A expression levels. Silencing miR-34b-5p or overexpressing LMX1B/HIGD1A significantly reduced apoptosis, inflammation, and mitochondrial dysfunction in both cell and animal models. Mechanistically, miR-34b-5p directly targeted LMX1B, suppressing HIGD1A transcription and exacerbating renal injury. Conclusion: Targeting the miR-34b-5p/LMX1B/HIGD1A axis offers a novel biotechnological strategy for the treatment of sepsis-induced AKI. This work provides a robust molecular foundation for advancing miRNA-based therapeutics.
Source: PubMed Central
Authors: Hong Shao, Sheng Xu, Bin Du, Yafang Chen
Institution: Jiaxing University
Language: English
Topic: Acute Kidney Injury Research
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7223670867