A crucial role of bone morphogenetic protein signaling in the wound healing response in acute liver injury induced by carbon tetrachloride

骨形态发生蛋白信号在四氯化碳引起的急性肝损伤伤口愈合反应中起着至关重要的作用

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作者:Nao Oumi, Kumiko Amano Taniguchi, Ayumi Miyashita Kanai, Mayu Yasunaga, Tomoko Nakanishi, Kenzo Sato

Abstract

Background. Acute liver injury induced by administration of carbon tetrachloride (CCl(4)) 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 CCl(4) 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 CCl(4)-treated liver. Results. We observed retardation of the healing response in the knockout mice treated with CCl(4), 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.

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