Increased production of ADAMTS13 in hepatic stellate cells contributes to enhanced plasma ADAMTS13 activity in rat models of cholestasis and steatohepatitis

Naoko Watanabe; Hitoshi Ikeda; Yukio Kume; Yumiko Satoh; Makoto Kaneko; Daiya Takai; Kazuaki Tejima; Masakazu Nagamine; Hirosato Mashima; Tomoaki Tomiya; Eisei Noiri; Masao Omata; Masanori Matsumoto; Yoshihiro Fujimura; Yutaka Yatomi

doi:10.1160/TH08-11-0732

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2009; 102(02): 389-396
DOI: 10.1160/TH08-11-0732

Animal Models

Schattauer GmbH

Increased production of ADAMTS13 in hepatic stellate cells contributes to enhanced plasma ADAMTS13 activity in rat models of cholestasis and steatohepatitis

Authors

Naoko Watanabe

¹Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo Japan

²Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Hitoshi Ikeda

¹Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo Japan

²Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Yukio Kume

¹Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo Japan
Yumiko Satoh

¹Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo Japan
Makoto Kaneko

¹Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo Japan
Daiya Takai

¹Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo Japan
Kazuaki Tejima

¹Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo Japan

²Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Masakazu Nagamine

¹Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo Japan
Hirosato Mashima

²Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Tomoaki Tomiya

²Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Eisei Noiri

³Department of Hemodialysis and Apheresis, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Masao Omata

²Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Masanori Matsumoto

⁴Department of Blood Transfusion Medicine, Nara Medical University, Nara, Japan
Yoshihiro Fujimura

⁴Department of Blood Transfusion Medicine, Nara Medical University, Nara, Japan
Yutaka Yatomi

¹Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo Japan

Abstract

Summary

Although hepatic stellate cells, endothelial cells, glomerular podocytes and plateles were reported to be a source of ADAMTS13, it is not clarified which source is involved in the regulation of plasma ADAMTS13 activity. It was demonstrated previously that selective hepatic stellate cell damage in rats caused decreased plasma ADAMTS13 activity.To further elucidate the potential contribution of hepatic stellate cells to the regulation of plasma ADAMTS13 activity, this study examined plasma ADAMTS13 activity when hepatic stellate cells proliferate during the process of liver fibrosis by employing rat models of liver fibrosis due to cholestasis, bile duct ligation, and steatohepatitis, a choline-deficient L-amino acid-defined-diet. ADAMTS13 expression was increased with co-localisation with smooth muscle α-actin, a marker of hepatic stellate cells, in bile duct-ligated livers up to four weeks, in which a close correlation between ADAMTS13 and smooth muscle α-actin mRNA expressions was determined. Plasma ADAMTS13 activity, measured by a sandwich ELISA involving a specific substrate to ADAMTS13, was increased in bile duct-ligated rats with a significant correlation with ADAMTS13 mRNA expression levels in the liver. Furthermore, ADAMTS13 mRNA expression was increased with enhanced mRNA expression in smooth muscle α-actin in the livers of rats fed a choline-deficient L-amino aciddefined-diet for 16 weeks, in which increased plasma ADAMTS13 activity was determined. Thus, increased plasma ADAMTS13 activity in cholestasis and steatohepatitis in rats may be due, at least in part, to enhanced ADAMTS13 production in the liver, suggesting a significant role of hepatic stellate cells in the regulation of plasma ADAMTS13 activity.

Keywords

ADAMTS13 - hepatic stellate cell - smooth muscle α-actin - bile duct ligation - steatohepatitis

Volltext

Referenzen

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