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Peer-reviewedCC BY-NCIranian journal of biotechnology

MicroRNA-34b-5p Modulates Sepsis-Induced Acute Kidney Injury via the LMX1B/HIGD1A Axis: Implications for Molecular Therapeutics.

  1. 1Department of Intensive Care Unit, The Third Affiliated Hospital of Jiaxing University (Zhejiang Rongjun Hospital), Zhejiang 314000, China.

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.

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BibTeX
@article{shao2026microrna34b5p,
  title = {{MicroRNA-34b-5p Modulates Sepsis-Induced Acute Kidney Injury via the LMX1B/HIGD1A Axis: Implications for Molecular Therapeutics.}},
  author = {Hong Shao and Sheng Xu and Bin Du and Yafang Chen},
  journal = {Iranian journal of biotechnology},
  year = {2026},
  month = oct,
  doi = {10.30498/ijb.2026.513356.4095},
  url = {https://europepmc.org/article/MED/42928727},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - MicroRNA-34b-5p Modulates Sepsis-Induced Acute Kidney Injury via the LMX1B/HIGD1A Axis: Implications for Molecular Therapeutics.
AU  - Hong Shao
AU  - Sheng Xu
AU  - Bin Du
AU  - Yafang Chen
PY  - 2026
DA  - 2026/10/01
JO  - Iranian journal of biotechnology
DO  - 10.30498/ijb.2026.513356.4095
UR  - https://europepmc.org/article/MED/42928727
AB  - 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.
SN  - 1728-3043
SN  - 2322-2921
ER  -