[microRNA-34a participates in lipopolysaccharide mediated sepsis related renal function impairment via Kruppel-like
Qidong Jiang1, Changxue Wu, Qiong Zhang
1Department of Intensive Care Unit, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China (Jiang QD, Wu CX); Department of Nephrology, the Second Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China (Zhang Q). Corresponding author: Zhang Qiong,
Objective:
To investigate whether microRNA-34a (miR-34a) participates in lipopolysaccharide (LPS) mediated sepsis related renal function impairment via Kruppel-like factor 4 (KLF4).
Methods:
Thirty healthy male Sprague-Dawley (SD) rats, weighing 180-200 g, were randomly divided into two groups: control group and model group, with 15 rats in each group. The SD rats from model group were injected with LPS 7.5 mg/kg to induce sepsis related renal function impairment model, the SD rats from control group were injected with normal saline. The serum creatinine concentration (SCr) and blood urine nitrogen (BUN) content was detected by multifunction biochemical analyzer; the morphological changes of renal tissue were observed by hematoxylin and eosin stain (HE) staining; the expression of miR-34a and KLF4 gene in plasma and renal tissue were detected by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR); the protein expression of KLF4 in renal tissue was detected by Western Blot; the target gene of miR-34a was verified by double luciferase reporter gene analysis.
Results:
Compared with control group, inflammatory cell infiltration in renal tissue was increased in model group, the SCr and BUN were significantly increased [SCr (μmol/L): 142.5±10.6 vs. 46.4±5.6, BUN (mmol/L): 31.6±6.2 vs. 8.5±1.2, both P < 0.01], the gene expression of miR-34 in plasma and renal tissue were significantly increased (2-ΔΔCt: 2.26±0.11 vs. 1.14±0.05 in plasma, 4.23±0.12 vs. 1.12±0.04 in renal tissue, both P < 0.01), the gene and protein expressions of KLF4 were significantly decreased [KLF4 gene (2-ΔΔCt): 0.52±0.03 vs. 1.21±0.06, KLF4 protein (A value): 0.72±0.03 vs. 1.05±0.04, both P < 0.01], which indicated that kidney injury occurred in rats. Pearson correlation analysis showed that plasma miR-34a was positively correlated with SCr and BUN (r value were 0.678, 0.721, respectively, both P < 0.05). Double luciferase reporter assay confirmed that KLF4 was the target gene of miR-34a.
Conclusions:
The miR-34a participates in LPS mediated sepsis related renal function impairment via KLF4.
Insights
MicroRNA-34a (miR-34a) exacerbates sepsis-induced kidney damage by downregulating Kruppel-like factor 4 (KLF4). This study reveals miR-34a as a key player in sepsis-related renal dysfunction.
Area of Science:
- Biomedical research
- Molecular biology
- Renal pathophysiology
Background:
- Sepsis-related acute kidney injury (AKI) is a critical clinical challenge.
- MicroRNAs (miRNAs) are increasingly recognized as regulators of cellular processes and disease.
- The role of specific miRNAs, like miR-34a, in sepsis-induced kidney dysfunction requires further elucidation.
Purpose of the Study:
- To investigate the role of microRNA-34a (miR-34a) in lipopolysaccharide (LPS)-induced sepsis and subsequent renal function impairment.
- To determine if miR-34a mediates renal dysfunction through its interaction with Kruppel-like factor 4 (KLF4).
Main Methods:
- A rat model of sepsis-induced renal dysfunction was established using lipopolysaccharide (LPS) injection.
- Renal function was assessed by measuring serum creatinine (SCr) and blood urea nitrogen (BUN).
- Expression levels of miR-34a and KLF4 were quantified using qRT-PCR and Western Blot. Target validation was performed using a dual-luciferase reporter assay.
Main Results:
- LPS-induced sepsis significantly increased inflammatory cell infiltration, SCr, and BUN levels, indicating kidney injury.
- miR-34a expression was significantly upregulated in plasma and renal tissue of septic rats.
- KLF4 gene and protein expression were significantly downregulated, and KLF4 was confirmed as a direct target of miR-34a. Plasma miR-34a levels positively correlated with SCr and BUN.
Conclusions:
- MicroRNA-34a plays a significant role in the pathogenesis of lipopolysaccharide-mediated sepsis-related renal function impairment.
- The mechanism involves the downregulation of Kruppel-like factor 4 (KLF4) by miR-34a.
- miR-34a represents a potential therapeutic target for sepsis-induced kidney injury.
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