Abstract
It is very important to clarify the mechanism of acute lung injury and lung fibrosis after acute injury. High Mobility Group Box 1 (HMGB1) , in addition to its role as a transcriptional regulatory factor, has recently been identified as a late mediator of endotoxin lethality. HMGB1 was also reported to induce lung injury in septic state. Here we show that blocking HMGB1 signal tranduction by treatment of the antibody for RAGE, which is the main receptor for HMGB1. This promotes LPS-challenged mice survival and improves acute lung injury. Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone and is essential for collagen maturation in the ER. In the absence of HSP47, tissue fibrosis after injury is impaired because of failure in the molecular maturation of collagens. HSP47 antisense, which can block HSP47 translation, was administered in bleomycin-treated rats. HSP47 antisense can dramatically block lung fibrosis and improve survival rate. These results suggest that blocking HMGB1 signal tranduction is very effective for the treatment of acute phase lung injury and blocking HSP47 translation can also reduce lung fibrosis in the process of lung tissue remodeling.
