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

To investigate the role and mechanism of fibrinogen-like protein 2（Fgl2）in acute kidney injury induced by rhabdomyolysis（RM-AKI）.

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.

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.

Knockout of Fgl2 inhibits inflammatory response and reduces apoptosis in renal cells, and exerts a protective effects on RM-AKI mice.