2. Academic Validation
  3. Identification and validation of leukemia inhibitory factor as a protective factor in ischemic acute kidney injury

Identification and validation of leukemia inhibitory factor as a protective factor in ischemic acute kidney injury

  • Am J Med Sci. 2025 Apr;369(4):524-536. doi: 10.1016/j.amjms.2024.09.010.
Lemei Hu 1,  Chen Jiao 1,  Haiyu Gu 2,  Zhigang Zhu 3,  Ming Liang 4
Affiliations

Affiliations

  • 1 Department of Nephrology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Panfu Road, Guangzhou, Guangdong 510000, China.
  • 2 Department of Emergency Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong 510180, China.
  • 3 Division of Hematology & Oncology, Department of Geriatrics, Second Affiliated Hospital, Guangzhou First People's Hospital, College of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, China.
  • 4 Department of Nephrology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Panfu Road, Guangzhou, Guangdong 510000, China. Electronic address: [email protected].
PMID: 39313116 DOI: 10.1016/j.amjms.2024.09.010
Abstract

Background: Ischemia-reperfusion injury (IRI) is a common pathophysiological mechanism of acute kidney injury (AKI). There is an urgent need for a more comprehensive analysis of its underlying mechanisms.

Materials and methods: The RNA-sequencing dataset GSE153625 was used to examine differentially expressed genes (DEGs) of kidney tissues in IRI-AKI mice compared with sham mice. We used 10 algorithms provided by cytohubba plugin and four external datasets (GSE192532, GSE52004, GSE98622, and GSE185383) to screen for hub genes. The IRI-AKI mouse model with different reperfusion times was established to validate the expression of hub gene in the kidneys. HK-2 cells were cultured in vitro under hypoxia/reoxygenation (H/R) conditions, via transfection with si-LIF or supplementation with the LIF protein to explore the function of the LIF gene.

Results: We screened a total of 1,540 DEGs in the IRI group compared with the sham group and identified that the LIF hub gene may play potential roles in IRI-AKI. LIF was markedly upregulated in the kidney tissues of IRI-AKI mice, as well as in HK-2 cells grown under H/R conditions. The knockdown of LIF aggravated Apoptosis and oxidative stress (OS) injury under H/R conditions. Administration of the LIF protein rescued the effects of si-LIF, alleviating cellular Apoptosis and OS.

Conclusion: These findings indicate an important role of the LIF gene in term of regulating Apoptosis and OS in the early phases of IRI-AKI. Targeting LIF may therefore represent a promising therapeutic strategy for IRI-AKI.

Keywords

Acute kidney injury; HK-2 cell; Ischemia-reperfusion injury; Leukemia inhibitory factor.

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