TIMP-1 is upregulated, but not essential in hepatic fibrogenesis and carcinogenesis in mice

Abstract Tissue inhibitor of metalloproteinases-1 (TIMP-1) is upregulated during hepatic fibrogenesis and considered to promote fibrosis in the injured liver by inhibition of matrix metalloproteases (MMP) and degradation of extracellular matrix. Moreover, TIMP-1 displays anti-apoptotic properties, i...

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Autores principales:	Nina D. Thiele, Jan W. Wirth, David Steins, Anja C. Koop, Harald Ittrich, Ansgar W. Lohse, Johannes Kluwe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8249ec5cf9c64388b217d23bbe7ada54
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spelling	oai:doaj.org-article:8249ec5cf9c64388b217d23bbe7ada542021-12-02T12:32:08ZTIMP-1 is upregulated, but not essential in hepatic fibrogenesis and carcinogenesis in mice10.1038/s41598-017-00671-12045-2322https://doaj.org/article/8249ec5cf9c64388b217d23bbe7ada542017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00671-1https://doaj.org/toc/2045-2322Abstract Tissue inhibitor of metalloproteinases-1 (TIMP-1) is upregulated during hepatic fibrogenesis and considered to promote fibrosis in the injured liver by inhibition of matrix metalloproteases (MMP) and degradation of extracellular matrix. Moreover, TIMP-1 displays anti-apoptotic properties, in patients with hepatocellular carcinoma (HCC) TIMP-1 serum levels are elevated and high TIMP-1 expression levels in HCC are associated with a poor prognosis. Therefore, TIMP-1 could functionally link fibrogenesis and carcinogenesis in the liver. The aim of our study was to characterize the role of TIMP-1 in hepatic fibrogenesis and carcinogenesis. Experimental hepatic fibrogenesis as well as diethylnitrosamine (DEN) -induced hepatocarcinogenesis were studied in TIMP-1-deficient mice and wild type littermates. Hepatic TIMP-1 expression was upregulated following induction of liver fibrosis by bile duct ligation (BDL) or by carbon tetrachloride (CCl4). Unexpectedly, in comparison to wild type littermates, TIMP-1-deficient mice were not protected from liver fibrosis induced by BDL or CCl4. TIMP-1 expression was significantly higher in HCC nodules than in surrounding liver tissue. However, experimental hepatic carcinogenesis was similar in TIMP-1-deficient mice and wild type littermates following DEN-treatment or combined treatment with DEN and CCl4. Therefore we concluded that TIMP-1 is not essential for hepatic fibrogenesis and carcinogenesis in mice.Nina D. ThieleJan W. WirthDavid SteinsAnja C. KoopHarald IttrichAnsgar W. LohseJohannes KluweNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nina D. Thiele Jan W. Wirth David Steins Anja C. Koop Harald Ittrich Ansgar W. Lohse Johannes Kluwe TIMP-1 is upregulated, but not essential in hepatic fibrogenesis and carcinogenesis in mice
description	Abstract Tissue inhibitor of metalloproteinases-1 (TIMP-1) is upregulated during hepatic fibrogenesis and considered to promote fibrosis in the injured liver by inhibition of matrix metalloproteases (MMP) and degradation of extracellular matrix. Moreover, TIMP-1 displays anti-apoptotic properties, in patients with hepatocellular carcinoma (HCC) TIMP-1 serum levels are elevated and high TIMP-1 expression levels in HCC are associated with a poor prognosis. Therefore, TIMP-1 could functionally link fibrogenesis and carcinogenesis in the liver. The aim of our study was to characterize the role of TIMP-1 in hepatic fibrogenesis and carcinogenesis. Experimental hepatic fibrogenesis as well as diethylnitrosamine (DEN) -induced hepatocarcinogenesis were studied in TIMP-1-deficient mice and wild type littermates. Hepatic TIMP-1 expression was upregulated following induction of liver fibrosis by bile duct ligation (BDL) or by carbon tetrachloride (CCl4). Unexpectedly, in comparison to wild type littermates, TIMP-1-deficient mice were not protected from liver fibrosis induced by BDL or CCl4. TIMP-1 expression was significantly higher in HCC nodules than in surrounding liver tissue. However, experimental hepatic carcinogenesis was similar in TIMP-1-deficient mice and wild type littermates following DEN-treatment or combined treatment with DEN and CCl4. Therefore we concluded that TIMP-1 is not essential for hepatic fibrogenesis and carcinogenesis in mice.
format	article
author	Nina D. Thiele Jan W. Wirth David Steins Anja C. Koop Harald Ittrich Ansgar W. Lohse Johannes Kluwe
author_facet	Nina D. Thiele Jan W. Wirth David Steins Anja C. Koop Harald Ittrich Ansgar W. Lohse Johannes Kluwe
author_sort	Nina D. Thiele
title	TIMP-1 is upregulated, but not essential in hepatic fibrogenesis and carcinogenesis in mice
title_short	TIMP-1 is upregulated, but not essential in hepatic fibrogenesis and carcinogenesis in mice
title_full	TIMP-1 is upregulated, but not essential in hepatic fibrogenesis and carcinogenesis in mice
title_fullStr	TIMP-1 is upregulated, but not essential in hepatic fibrogenesis and carcinogenesis in mice
title_full_unstemmed	TIMP-1 is upregulated, but not essential in hepatic fibrogenesis and carcinogenesis in mice
title_sort	timp-1 is upregulated, but not essential in hepatic fibrogenesis and carcinogenesis in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8249ec5cf9c64388b217d23bbe7ada54
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TIMP-1 is upregulated, but not essential in hepatic fibrogenesis and carcinogenesis in mice

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