Effects of mesencephalic astrocyte-derived neurotrophic factor on sepsis-associated acute kidney injury

Saifeng Chen; Xuewei Hao; Guo Chen; Guorong Liu; Xiaoyan Yuan; Peiling Shen; Dongfeng Guo

doi:10.5847/wjem.j.1920-8642.2023.077

Effects of mesencephalic astrocyte-derived neurotrophic factor on sepsis-associated acute kidney injury

World J Emerg Med. 2023;14(5):386-392. doi: 10.5847/wjem.j.1920-8642.2023.077.

Authors

Saifeng Chen^{1

2}, Xuewei Hao¹, Guo Chen², Guorong Liu², Xiaoyan Yuan², Peiling Shen², Dongfeng Guo^{1

2}

Affiliations

¹ Postgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical College, Shanghai 200135, China.
² Department of Emergency Medicine, Shanghai Gongli Hospital, Shanghai 200135, China.

Abstract

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.

Keywords: Cytokines; Endoplasmic reticulum stress; Mesencephalic astrocyte-derived neurotrophic factor; Renal function; Sepsis-associated acute kidney injury.