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Published on: February 15, 2022
Effects of mesencephalic astrocyte-derived neurotrophic factor on sepsis-associated acute kidney injury
Saifeng Chen1,2, Xuewei Hao1, Guo Chen2
1Postgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical College, Shanghai 200135, China.
Background:
To determine the protective role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in regulating sepsis-associated acute kidney injury (S-AKI).
Methods:
A total of 96 mice were randomly divided into the control group, control+MANF group, S-AKI group, and S-AKI+MANF group. The S-AKI model was established by injecting lipopolysaccharide (LPS) at 10 mg/kg intraperitoneally. MANF (200 μg/kg) was administered to the control+MANF and S-AKI+MANF groups. An equal dose of normal saline was administered daily intraperitoneally in the control and S-AKI groups. Serum and kidney tissue samples were obtained for biochemical analysis. Western blotting was used to detect the protein expression of MANF in the kidney, and enzyme-linked immunosorbent assay (ELISA) was used to determine expression of MANF in the serum, pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]). Serum creatinine (SCr), and blood urea nitrogen (BUN) were examined using an automatic biochemical analyzer. In addition, the kidney tissue was observed for pathological changes by hematoxylin-eosin staining. The comparison between two groups was performed by unpaired Student's t-test, and statistics among multiple groups were carried out using Tukey's post hoc test following one-way analysis of variance (ANOVA). A P-value <0.05 was considered statistically significant.
Results:
At the early stage of S-AKI, MANF in the kidney tissue was up-regulated, but with the development of the disease, it was down-regulated. Renal function was worsened in the S-AKI group, and TNF-α and IL-6 were elevated. The administration of MANF significantly alleviated the elevated levels of SCr and BUN and inhibited the expression of TNF-α and IL-6 in the kidney. The pathological changes were more extensive in the S-AKI group than in the S-AKI+MANF group.
Conclusion:
MANF treatment may significantly alleviate renal injury, reduce the inflammatory response, and alleviate or reverse kidney tissue damage. MANF may have a protective effect on S-AKI, suggesting a potential treatment for S-AKI.
Insights
Mesencephalic astrocyte-derived neurotrophic factor (MANF) shows protective effects against sepsis-associated acute kidney injury (S-AKI). MANF treatment alleviated kidney damage and reduced inflammation, suggesting its potential as a therapeutic agent for S-AKI.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Sepsis-associated acute kidney injury (S-AKI) is a critical condition with significant morbidity and mortality.
- The role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in the pathogenesis and potential treatment of S-AKI remains to be fully elucidated.
Purpose of the Study:
- To investigate the protective role of MANF in a mouse model of S-AKI.
- To assess the impact of MANF administration on renal function, inflammatory markers, and kidney histopathology in S-AKI.
Main Methods:
- A sepsis-associated acute kidney injury (S-AKI) model was established in mice using lipopolysaccharide (LPS).
- Mice were treated with mesencephalic astrocyte-derived neurotrophic factor (MANF) or saline.
- Renal function (serum creatinine, BUN), inflammatory cytokines (TNF-α, IL-6), and kidney histopathology were assessed.
Main Results:
- Sepsis-associated acute kidney injury (S-AKI) led to worsened renal function and elevated pro-inflammatory cytokines.
- Mesencephalic astrocyte-derived neurotrophic factor (MANF) administration significantly reduced serum creatinine and BUN levels.
- MANF treatment inhibited the expression of TNF-α and IL-6 and attenuated kidney tissue damage in S-AKI mice.
Conclusions:
- Mesencephalic astrocyte-derived neurotrophic factor (MANF) demonstrates a significant protective effect against sepsis-associated acute kidney injury (S-AKI).
- MANF treatment alleviates renal injury, reduces the inflammatory response, and mitigates kidney tissue damage.
- MANF represents a potential therapeutic strategy for managing S-AKI.
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