Lumican overexpression exacerbates lipopolysaccharide-induced renal injury in mice

Lu,Xiao‑Mei; Ma,Ling; Jin,Yu‑Nan; Yu,Yan‑Qiu

doi:10.3892/mmr.2015.3940

Lumican overexpression exacerbates lipopolysaccharide-induced renal injury in mice

Authors:
- Xiao‑Mei Lu
- Ling Ma
- Yu‑Nan Jin
- Yan‑Qiu Yu
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Affiliations: Department of Pathophysiology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: June 16, 2015 https://doi.org/10.3892/mmr.2015.3940
Pages: 4089-4094
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The present study aimed to investigate the role of lumican in mice with endotoxin-induced acute renal failure (ARF). Lumican transgenic mice and wild‑type mice were injected with lipopolysaccharide (LPS; 10 mg/kg) to establish a model of ARF. The mice were sacrificed at 24 h and the blood and renal tissue samples were collected. The value of serum creatinine (SCr) and blood urea nitrogen (BUN) were measured to determine renal function. An ELISA was used to determined the concentrations of renal cytokines, including tumor necrosis factor (TNF)α, interleukin (IL)‑6, IL‑4 and IL‑10. The protein expression levels of Toll-like receptor (TLR4) and nuclear factor (NF)κB in renal tissues were assessed using western blot analysis. Terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling was performed to monitor apoptosis of renal tissue. Light microscopy and electron microscopy were used to observe structural changes in the renal tissues. Following the administration of LPS, the SCr and BUN values of mice in the lumican transgenic group were higher compared with those in the control group. The expression levels of renal TLR4, NFκB, TNFα, IL‑6, IL‑4 and IL‑10 were upregulated in the lumican transgenic mice compared with those in the wild‑type control group. Apoptosis was detected predominantly on the renal tubule. There was a significant difference in the optical density of apoptotic bodies between the control mice and the lumican transgenic mice. Light and electron microscopy demonstrated more severe renal tissue injury in the lumican transgenic mice compared with that in the control mice. In conclusion, LPS may cause excessive apoptosis in the renal tubular cells via the TLR4 signal transduction pathway, a decrease in the number of renal tubular cells and ARF. Lumican may be important in mice with LPS-induced ARF.

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