A Crucial Role of Bone Morphogenetic Protein Signaling in the Wound Healing Response in Acute Liver Injury Induced by Carbon Tetrachloride

摘要

Background.Acute liver injury induced by administration of carbon tetrachloride (CCl4) has used a model of wound repair in the rat liver. Previously, we reported transient expression of bone morphogenetic protein (Bmp) 2 or Bmp4 at 6–24 h after CCl4treatment, suggesting a role of BMP signaling in the wound healing response in the injured liver. In the present study, we investigated the biological meaning of the transientBmpexpression in liver injury.Methods.Using conditional knockout mice carrying a floxed exon in the BMP receptor 1A gene, we determined the hepatic gene expressions and proliferative activity following CCl4-treated liver.Results.We observed retardation of the healing response in the knockout mice treated with CCl4, including aggravated histological feature and reduced expressions of thealbuminandTdo2genes, and a particular decrease in the proliferative activity shown by Ki-67 immunohistochemistry.Conclusion.Our findings suggest a crucial role of BMP signaling in the amelioration of acute liver injury.