title: Hepatic fibrosis and angiogenesis after bile duct ligation are endogenously expressed vasohibin-1 independent.
abstract: Liver fibrosis is linked to VEGF-induced angiogenesis. Overexpression of exogenous vasohibin-1, a feedback inhibitor of angiogenesis, has been reported to reduce liver fibrosis after bile duct ligation (BDL). To uncover the function of endogenous vasohibin-1, we performed BDL using vasohibin-1-deficient mice and analyzed liver fibrosis, injury, and angiogenesis. Liver fibrosis was induced by 14-days of BDL in both wild-type and vasohibin-1-deficient mice. The liver sections were stained with anti-CD31 to visualize endothelial cells and with Sirius red to observe fibrotic regions. Total RNAs were purified from the livers and expression of collagen I α1 mRNA was measured by quantitative PCR. Plasma ALT activity was determined to assess liver injury. Surprisingly, the same extents of increases were seen in anti-CD31 and Sirius red stainings, collagen I α1 mRNA expressions, hepatic hydroxyproline contents, and ALT activity after 14-days of BDL in both wild-type and vasohibin-1-deficient mice. There was unexpectedly no difference between these mice, suggesting that anti-fibrogenic and angiogenic activities of the endogenous vasohibin-1 might be masked in the normal liver at early stage of hepatic fibrosis in mice.
authors.affiliation: Micro-Signaling Regulation Technology Unit, RIKEN Center for Life Science Technologies, Saitama, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Furutani
authors.affiliation: Micro-Signaling Regulation Technology Unit, RIKEN Center for Life Science Technologies, Saitama, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Shiozaki-Sato
authors.affiliation: Micro-Signaling Regulation Technology Unit, RIKEN Center for Life Science Technologies, Saitama, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Hara
authors.affiliation: Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Micro-Signaling Regulation Technology Unit, RIKEN Center for Life Science Technologies, Saitama, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: skojima@riken.jp.
authors.forename: Soichi
authors.initials: S
authors.lastname: Kojima
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D018797:Cell Cycle Proteins / Q000235:genetics*; D055786:Gene Knockout Techniques; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000150:complications / Q000235:genetics* / Q000473:pathology*
chemical_list: D018797:Cell Cycle Proteins; C510089:Vash1 protein, mouse
keywords: Angiogenesis; Bile duct ligation; Fibrosis; Liver; Vasohibin-1