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Thromb Haemost 2010; 104(03): 531-533
DOI: 10.1160/TH09-12-0860
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

A splice variant of ADAMTS13 is expressed in human hepatic stellate cells and cancerous tissues

Noam Shomron   #
1   Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Nobuko Hamasaki-Katagiri   #
2   Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA
,
Ryan Hunt
2   Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA
,
Klilah Hershko
2   Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA
,
Elie Pommier
2   Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA
,
S. Geetha
2   Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA
,
Adam Blaisdell
2   Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA
,
Andrew Marple
3   Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
,
Isabella Roma
3   Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
,
Jordan Newell
2   Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA
,
Courtni Allen
2   Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA
,
Scott Friedman
4   Division of Liver Diseases, Mount Sinai School of Medicine, New York, New York, USA
,
Chava Kimchi-Sarfaty
2   Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA
› Author Affiliations
Further Information

Publication History

Received: 23 December 2009

Accepted after major revision: 06 May 2010

Publication Date:
23 November 2017 (online)

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Summary

Although ADAMTS13, the von Willebrand factor (VWF)-cleaving protease, is expressed in a range of tissues, the physiological significance of tissue-specific ADAMTS13 alternative splicing isoforms have yet to be clarified. Screening a panel of human tissues and cell lines revealed a spliced ADAMTS13 transcript in hepatic stellate cells and a hepatoma cell line that retains the 25th intron. A nonsense codon within the intron truncates the protease, which gains 64 novel amino acids in lieu of both CUB domains. This isoform, while retaining VWF-cleaving capability, accumulates intracellularly and its biological inaccessibility may prevent its participation in regulating haemostasis and other physiologic functions.

Keywords

ADAMTS13 - alternative splicing - intron retention - TTP - CUB domain

# These authors contributed equally to the research in this manuscript.


 

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