Role and mechanism of Fgl2 in rhabdomyolysis-induced acute kidney injury in mice

Abstract

Objective To investigate the role and mechanism of fibrinogen-like protein 2 (Fgl2) in acute kidney injury induced by rhabdomyolysis (RM-AKI). Methods Wild-type mice (WT) and Fgl2 gene knockout mice (Fgl2 KO) with the same background, were randomly divided into 4 groups respectively, that is WT+saline, WT+Gly, Fgl2 KO+saline, Fgl2 KO+Gly (n=5). The mice of the RM-AKI group were given 50% glycerol (10 μL/g) and those of the control groups were given same amount of normal saline into the hind leg by intramuscular injection. In 48 h later, the serum samples were collected to detect the levels of Scr and BUN. HE staining was employed to assess and score the severity of renal injury. qRT-PCR was used to detect the mRNA levels of Fgl2, IL-6, MCP-1, TNF-α, IL-1β and IL-10. The expression of Fgl2 and F4/80 was observed with immunohistochemical staining (IHC). TUNEL assay and Western blotting were applied to measure cell apoptosis and expression of apoptosis-related proteins, respectively. Results Fgl2 expression in renal tissue was significantly elevated in glycerol-treated WT mice compared with saline-treated WT mice. When compared with WT mice, Fgl2 deficiency significantly alleviated renal dysfunction and renal histopathological injury, with statistically lower renal injury score (P < 0.05). Moreover, the expression of pro-inflammatory factors, IL-6, MCP-1, TNF-α and IL-1β in renal tissues was decreased, while that of anti-inflammatory factor IL-10 was increased (P < 0.05). The infiltration of macrophages and apoptosis of renal cells were reduced in the Fgl2 KO mice than the WT mice. The expression of apoptosis-related proteins, Bax, cleaved Caspase-3, and cleaved Caspase-9 was reduced, while that of Bcl2 showed no significant difference. Conclusion Knockout of Fgl2 inhibits inflammatory response and reduces apoptosis in renal cells, and exerts a protective effects on RM-AKI mice.

Keywords

• fibrinogen-like protein 2
• rhabdomyolysis
• acute kidney injury
• inflammatory response
• cell apoptosis