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

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 CCl4 treatment, 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 transient Bmp expression 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 the albumin and Tdo2 genes, 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

Induction of Hepatocyte Nuclear Factor 3γ Gene Expression by the Extracellular Matrix Component from Fish Skin

The skin of the halibut (Reinhararditus hippoglossoides) has long been discarded as a waste product by the food industry in large quantities; hence, we examined the biological activity in the skin for utilization of the waste. In the present study, we determined induction of hepatocyte nuclear factor 3γ (HNF3γ), which is involved in liver function, using human hepatoma cell line HepG2 and extracellular matrix components extracted from the fish skin. Induction of the HNF3γ was detected by reporter plasmid constructed with the promoter region of the HNF3γ gene and luciferase or green fluorescent protein genes. The alkali extract containing proteoglycan showed HNF3γ induction, but the acid-extract enriched in collagen did not. Consequently, dermatan sulfate showed the strongest activity in HNF3γ induction. These observations suggested that fish skin has some significant biological activity, and indicates its possible function in the food and drug industry