JAML promotes acute kidney injury mainly through a macrophage-dependent mechanism.

Although macrophages are undoubtedly attractive therapeutic targets for acute kidney injury (AKI) because of their critical roles in renal inflammation and repair, the underlying mechanisms of macrophage phenotype switching and efferocytosis in the regulation of inflammatory responses during AKI are still largely unclear. The present study elucidated the role of junctional adhesion molecule-like protein (JAML) in the pathogenesis of AKI. We found that JAML was significantly upregulated in kidneys from 2 different murine AKI models including renal ischemia/reperfusion injury (IRI) and cisplatin-induced AKI. By generation of bone marrow chimeric mice, macrophage-specific and tubular cell-specific Jaml conditional knockout mice, we demonstrated JAML promoted AKI mainly via a macrophage-dependent mechanism and found that JAML-mediated macrophage phenotype polarization and efferocytosis is one of the critical signal transduction pathways linking inflammatory responses to AKI. Mechanistically, the effects of JAML on the regulation of macrophages were, at least in part, associated with a macrophage-inducible C-type lectin-dependent mechanism. Collectively, our studies explore for the first time to our knowledge new biological functions of JAML in macrophages and conclude that JAML is an important mediator and biomarker of AKI. Pharmacological targeting of JAML-mediated signaling pathways at multiple levels may provide a novel therapeutic strategy for patients with AKI.

[Antioxidant effects of the Uygur herb, Foeniculum Vulgare Mill, in a rat model of hepatic fibrosis].

OBJECTIVE: To evaluate therapeutic and antioxidant effects of Uygur Herb Foeniculum Vulgare Mill (FVM) in hepatic fibrosis rats. METHOD: Hepatic fibrosis model was built in rats by subcutaneous injection with 40% CCl4 olive oil mixture. At the same time the rats were given high lipoid-low protein animal feeds for 5 weeks. 94 male SD rats were randomly divided into six groups :blank control group (A-group), 8 rats were feed in normal; prevention model control group (B-group), 10 rats were given saline solution by intragastric administration during make of hepatic fibrosis model; FVM prevention group (C-group), 10 rats were given FVM by intragastric administration during make of hepatic fibrosis model; model control group (D-group), FVM treatment group (E-group); Fuzhenghuayu treatment group (F-group). 22 rats in each D, E, F-group were respectively given saline solution, FVM and Fuzhenghuayu by intragastric administration after hepatic fibrosis model were built. At the 5-th weekend, A, B, C- group rats were sacrificed. At the 6-th, 7-th, 8-th, 9-th weekend, 4-6 rats in D, E, F-group were sacrificed. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN) and 8 - hydroxy-2-deoxyguanosine (8-OHdG) were detected, liver tissue homogenate superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) were detected. Histopathologic changes were observed after H.E and Masson staining. The expression of alpha-smooth muscle actin(a-SMA) were detected by immunohistochemical staining. The data were analyzed by SPSS17.0 software. RESULTS: The serum levels of ALT, AST, HA, and LN in the FVM prevention group were significantly reduced compared to the prevention model control group.(P less than 0.05). Rats in FVM treatment group appeared a marked lower serum levels of ALT, AST, HA compared to the model control group (P less than 0.05), and a distinguished lower Inflammation grade and fibrosis stage (P less than 0.05) when the liver section were assayed as well; Rats in FVM treatment group and FVM prevention group had a conspicuous lower content of MDA, 8-OHdG, fibre and a-SMA expression (P less than 0.05), a significantly higher level of SOD, GSH-Px compared to those of in the model control groups. CONCLUSIONS: Foeniculum Vulgare Mill declines liver inflammation response ,and prevent the hepatic fibrosis progression,, this may be due to its effects of antioxidative results.