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CD28 deficiency attenuates primary blast-induced renal injury in mice via the PI3K/Akt signalling pathway
Ying Liu1, Y E Liu1, C C Tong1
1Emergency Medicine Department of General Hospital of Northern Theater Command, Laboratory of Rescue Center of Severe Wound and Trauma PLA, Shenyang, China.
Introduction:
Primary blast affects the kidneys due to direct shock wave damage and the production of proinflammatory cytokines without effective treatment. CD28 has been reported to be involved in regulating T cell activation and secretion of inflammatory cytokines. The aim of this study was to investigate the influence of primary blast on the kidney and the effect of CD28 in mice.
Methods:
A mouse model of primary blast-induced kidney injury was established using a custom-made explosive device. The severity of kidney injury was investigated by H&E staining. ELISA was applied to study serum inflammation factors' expression. Western blot assays were used to analyse the primary blast-induced inflammatory factors' expression in the kidney. Immunofluorescence analysis was used to examine the PI3K/Akt signalling pathway.
Results:
Histological examination demonstrated that compared with the primary blast group, CD28 deficiency caused a significant decrease in the severity of the primary blast-induced renal injury. Moreover, ELISA and western blotting revealed that CD28 deficiency significantly reduced the levels of interleukin (IL)-1β, IL-4 and IL-6, and increased the IL-10 level (p<0.05). Finally, immunofluorescence analysis indicated that PI3K/Akt expression also changed.
Conclusions:
CD28 deficiency had protective effects on primary blast-induced kidney injury via the PI3K/Akt signalling pathway. These findings improve the knowledge on primary blast injury and provide theoretical basis for primary blast injury treatment.
Insights
CD28 deficiency protects kidneys from primary blast injury by reducing inflammation and altering the PI3K/Akt pathway. This finding offers a potential therapeutic target for blast-induced renal damage.
Area of Science:
- Trauma research
- Immunology
- Renal pathophysiology
Background:
- Primary blast injury causes kidney damage via shock waves and inflammation.
- CD28 plays a role in T cell activation and inflammatory cytokine secretion.
- Effective treatments for blast-induced kidney injury are lacking.
Purpose of the Study:
- Investigate the impact of primary blast on kidney injury in mice.
- Determine the role of CD28 in modulating blast-induced renal damage.
Main Methods:
- Established a mouse model of primary blast-induced kidney injury.
- Assessed renal injury severity using H&E staining.
- Quantified inflammatory markers (IL-1β, IL-4, IL-6, IL-10) via ELISA and Western blot.
- Examined the PI3K/Akt signaling pathway using immunofluorescence.
Main Results:
- CD28 deficiency significantly reduced the severity of primary blast-induced kidney injury.
- CD28 deficiency decreased pro-inflammatory cytokines (IL-1β, IL-4, IL-6) and increased anti-inflammatory IL-10.
- Changes in PI3K/Akt signaling pathway expression were observed in CD28-deficient mice.
Conclusions:
- CD28 deficiency confers protection against primary blast-induced kidney injury.
- The protective mechanism involves modulation of the PI3K/Akt signaling pathway.
- Findings provide a theoretical basis for developing treatments for blast-induced renal injury.
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