Amelioration of collagen-induced arthritis in mice by lentivirus-mediated microRNA-223 silencing

Abstract Sepsis is a disease in which systemic inflammation-induced vascular leakage and disseminated intravascular coagulation lead to multiple organ failure. Despite a high mortality andmorbidity, there is currently no specific drug for sepsis. Thrombin, a serineprotease that mediates key sepsis-related pathologies, both activates coagulation cascades and acts as a mediator to induce vascular hyperpermeability and inflammation. It is known that thrombin can induce endothelial cells to secrete macrophage migration inhibitor factor (MIF) and MIFcan cause endothelial hyperpermeability via autophagy. However, it is unclearwhether MIF-induced autophagy is involved in thrombin-mediated vascular hyperpermeability. Herein, we show that thrombin treatment induced hyperpermeability, which was accompanied by VE-cadherin translocation in the human microvascular endothelial cell line (HMEC-1). Additionally, thrombin could induce MIF secretion and autophagy in HMEC-1 cells. Inhibition of MIF by its antibody or inhibitors could reduce thrombin-induced endothelial hyperpermeability and autophagy. However, inhibition of autophagy prevented only endothelial hyperpermeability, not MIF secretion. Finally, both MIF and autophagy inhibitors reduced thrombin- induced vascular leakage in vitro. Together, our data suggest that MIF-induced autophagy is involved in thrombin-mediated endothelial cell hyperpermeability. Further studies designed to test whether autophagy inhibitors could prevent endothelial barrier dysfunction in sepsis may provide potential therapeutic modalities to reduce sepsis-related mortality.

Endothelial Dysfunction

10.4049/jimmunol.196.supp.51.2

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SILDENAFIL ENHANCES DISTAL LUNG GROWTH AFTER TREATMENT WITH VEGF RECEPTOR INHIBITOR IN NEONATAL RATS

Acta Paediatrica (2009)

Yuh‐Jyh Lin Chyi‐Her Lin Chi-Hsien Chien Jiu‐Yao Wang

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543 Overexpression of Discoidin Domain Receptor 1 (DDR1) in Oral Squamous Cell Carcinoma

European Journal of Cancer (2012)