The gene products of two members of the EXT (exostosin) gene family, EXT1 and EXT2, function together as a polymerase in the biosynthesis of heparan sulfate. EXTL2 (EXT-like 2), one of the three EXTL genes in the human genome that are homologous to EXT1 and EXT2, encodes an N-acetylhexosaminyltransferase. We have demonstrated that EXTL2 terminates chain elongation of GAGs (glycosaminoglycans), and thereby regulates GAG biosynthesis. The abnormal GAG biosynthesis caused by loss of EXTL2 had no effect on normal development or normal adult homoeostasis. Therefore we examined the role of EXTL2 in CCl4 (carbon tetrachloride)-induced liver failure, a model of liver disease. On the fifth day after CCl4 administration, the liver/body weight ratio was significantly smaller for EXTL2-knockout mice than for wild-type mice. Consistent with this observation, hepatocyte proliferation following CCl4 treatment was lower in EXTL2-knockout mice than in wild-type mice. EXTL2-knockout mice experienced less HGF (hepatocyte growth factor)-mediated signalling than wild-type mice specifically because GAG synthesis was altered in these mutant mice. In addition, GAG synthesis in hepatic stellate cells was up-regulated during liver repair in EXTL2-knockout mice. Taken together, the results of the present study indicated that EXTL2-mediated regulation of GAG synthesis was important to the tissue regeneration processes that follow liver injury.
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Research Article|
July 26 2013
Roles of EXTL2, a member of the EXT family of tumour suppressors, in liver injury and regeneration processes
Satomi Nadanaka;
Satomi Nadanaka
1Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan
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Shoji Kagiyama;
Shoji Kagiyama
1Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan
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Hiroshi Kitagawa
Hiroshi Kitagawa
1
1Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
February 28 2013
Revision Received:
May 21 2013
Accepted:
June 04 2013
Accepted Manuscript online:
June 04 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 454 (1): 133–145.
Article history
Received:
February 28 2013
Revision Received:
May 21 2013
Accepted:
June 04 2013
Accepted Manuscript online:
June 04 2013
Citation
Satomi Nadanaka, Shoji Kagiyama, Hiroshi Kitagawa; Roles of EXTL2, a member of the EXT family of tumour suppressors, in liver injury and regeneration processes. Biochem J 15 August 2013; 454 (1): 133–145. doi: https://doi.org/10.1042/BJ20130323
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