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.

Experimental study of podophyllotoxin dipalmitoylphosphatidylcholine liposome for topical skin application.

OBJECTIVE: To observe the drug release of podophyllotoxin liposome and the drug retention in the skin. METHODS: Two liposome suspensions containing respectively podophyllotoxin dipalmitoylphosphatidylcholine (DPPC) and soya bean lecithin were prepared ultrasonically. Podophyllotoxin anhydride and the liposome suspensions were applied onto the skin of young pigs to observe the drug retention in the skin at different time points in the following 2 days, with exclusive liposome or anhydride serving as control. RESULTS: One hour after application of podophyllotoxin anhydride, a peak of the drug concentration in the skin occurred followed by immediate declination, a process not observed after the application of bean lecithin liposome due to gradual drug release that produced drug concentration constantly much higher than that of podophyllotoxin anhydride. A peak concentration was also observed 4 h after application of podophyllotoxin DPPC liposome, which then declined slowly to and stabilized at a higher level than that of bean lecithin liposome of anhydride within 48 h. CONCLUSION: DPPC liposome-embedded podophyllotoxin better targets the drug to the skin after application, and is a suitable preparation for topical skin application.