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@PHDTHESIS{Sterzer:707735,
author = {Sterzer, Viktor},
othercontributors = {Schirawski, Jan and Ludwig, Andreas},
title = {{D}er {E}influss von {E}ndoglin auf die {F}ibrose, sowie
die {I}nflammation und {R}egeneration in der {L}eber},
school = {RWTH Aachen University},
type = {Dissertation},
address = {Aachen},
reportid = {RWTH-2017-09397},
pages = {1 Online-Ressource (153 Seiten) : Illustrationen,
Diagramme},
year = {2017},
note = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
University; Dissertation, RWTH Aachen University, 2017},
abstract = {The aim of this thesis was to investigate the impact of
endoglin (Eng), an auxiliary transforming growth factor beta
(TGF-β) receptor on liver sinusoidal endothelial cells
(LSECs) on the liver fibrosis development. Additionally the
impact of endoglin on liver regeneration and -inflammation
in mice was investigated. Furthermore the role of endoglin
in the setting of nonalcoholic steatohepatitis (NASH) as
well as a nonalcoholic fat liver disease (NAFLD) combined
with an hepatocellular carcinoma (HCC) in human liver
biopsies should be elucidated. Methods: In the fibrosis
models Mice with an LSEC specific Eng knockout were injected
with carbon tetrachloride (CCl4) or a bile duct ligation
(BDL) was performed. In the liver regeneration and
-Inflammation experiments mice with an ubiquitary Eng
knockout were used. The liver regeneration was investigated
with a 2/3 partial hepatectomy model (p. H.), while the 1/3
ischemia-Reperfusion (I-R) technique was used as a model for
inflammation.Results: No differences could be observed in
the fibrosis grade between knockout and control animals in
the CCl4 as well as in the BDL model. Furthermore no
differences in the liver to bodyweight ratio in the p. H.
model were detectable. However, a trend to a higher
proliferation and a reduced triglyceride concentration as
well as a significant downregulation in the expression of
the fat transport proteins Fatp5 and Fabp1in the knockout
animals could be detected. In the I-R model slight
differences in the leukocyte infiltration but no differences
in the expression of inflammatory markers could be observed.
The analysis of the human liver biopsies revealed a
significant upregulation in the gene expression of ENG,
SERPINE-1 and ID1 in NASH patients.In the NAFLD/HCC group a
significant correlation between the expression of Eng and
the genes IFNG, TNF, CXCL16, TGFB, COL1A1, TIMP, GLI2, CD74,
CXCR4 and IL4 could be detected. There was no correlation
between Eng and the degree of steatosis in clinically
inconspicuous individuals.Conclusion: LSEC specific
expression of endoglin has neither an impact on the fibrosis
development in a CCl4 or BDL model respectively, nor has an
ubiquitary endoglin knockout an influence on the hepatic
inflammation or leukocyte infiltration in an I-R model.
Hepatic steatosis in humans does not correlate with the
endoglin expression, however endoglin could be involved in
the cell proliferation and fat transport processes according
to the results obtained in the p. H. experiments. The
results of the human liver biopsy gene expression analysis
allow the suggestion that endoglin could be involved in the
development of NASH as well as HCC. To fully unravel the
role of endoglin in these contexts further investigations
are needed.},
cin = {160000 / 161820},
ddc = {570},
cid = {$I:(DE-82)160000_20140620$ / $I:(DE-82)161820_20140620$},
typ = {PUB:(DE-HGF)11},
doi = {10.18154/RWTH-2017-09397},
url = {https://publications.rwth-aachen.de/record/707735},
}
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