Universität zu Köln

Borkham-Kamphorst, Erawan, Huss, Sebastian, Van de Leur, Eddy, Haas, Ute and Weiskirchen, Ralf ORCID: 0000-0003-3888-0931 (2012). Adenoviral CCN3/NOV gene transfer fails to mitigate liver fibrosis in an experimental bile duct ligation model because of hepatocyte apoptosis. Liver Int., 32 (9). S. 1342 - 1354. HOBOKEN: WILEY-BLACKWELL. ISSN 1478-3223

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Abstract

Background and Aims CCN3/NOV, a matricellular protein of the CYR61-CTGF-NOV (CCN) family, comprises six secreted proteins that associate specifically with the extracellular matrix. CCN proteins lack specific high-affinity receptors; instead, they regulate crucial biological processes, such as fibrosis, by signalling via integrins and proteoglycans. Recent studies have linked overexpression of CCN3/NOV to mitigate kidney fibrosis. This study aims to investigate CCN3/NOV overexpression in liver fibrogenesis in vivo. Methods The biological efficacy of adenoviral expressed CCN3/NOV directed under transcriptional control of the constitutively active Cytomegalovirus promoter (Ad-NOV) was analysed in a bile duct ligation model and in cultured primary hepatocytes. Results and Conclusions Even though Ad-NOV gene transfer in a 3-week bile duct ligation mouse model showed the expected high levels of CCN3/NOV in both mRNA and protein, it failed to reduce liver fibrogenesis, but instead enhanced hepatocyte apoptosis. Furthermore, overexpressed CCN3/NOV in cultured primary hepatocytes resulted in decreased levels of CCN2/CTGF, the profibrotic marker protein in liver fibrosis. Both Ad-NOV and Ad-CTGF induced reactive oxygen species production, enhanced p38 and JNK activation. Therefore, we conclude that CCN3/NOV overexpression in vivo is insufficient to mitigate liver fibrogenesis because of the induction of hepatocyte injury and apoptosis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Borkham-Kamphorst, Erawan UNSPECIFIED UNSPECIFIED UNSPECIFIED Huss, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Van de Leur, Eddy UNSPECIFIED UNSPECIFIED UNSPECIFIED Haas, Ute UNSPECIFIED UNSPECIFIED UNSPECIFIED Weiskirchen, Ralf UNSPECIFIED orcid.org/0000-0003-3888-0931 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-482506
DOI:	10.1111/j.1478-3231.2012.02837.x
Journal or Publication Title:	Liver Int.
Volume:	32
Number:	9
Page Range:	S. 1342 - 1354
Date:	2012
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1478-3223
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TISSUE GROWTH-FACTOR; EPITHELIAL-MESENCHYMAL TRANSITION; HEPATIC STELLATE CELLS; TGF-BETA; IN-VITRO; CONFERS RESISTANCE; RAT HEPATOCYTES; INJURED LIVER; EXPRESSION; MOUSE Multiple languages Gastroenterology & Hepatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48250