作者
Naoki Ikenaga, Zhen-Wei Peng, Kahini A Vaid, Susan B Liu, Shuhei Yoshida, Deanna Y Sverdlov, Amanda Mikels-Vigdal, Victoria Smith, Detlef Schuppan, Yury V Popov
发表日期
2017/9/1
期刊
Gut
卷号
66
期号
9
页码范围
1697-1708
出版商
BMJ Publishing Group
简介
Background/Aims
We studied the role of lysyl oxidase-like 2 (LOXL2) in collagen crosslinking and hepatic progenitor cell (HPC) differentiation, and the therapeutic efficacy of a LOXL2-blocking monoclonal antibody on liver fibrosis progression/reversal in mice.
Methods
Anti-LOXL2 antibody, control antilysyl oxidase antibody or placebo was administered during thioacetamide (TAA)-induced fibrosis progression or during recovery. Therapeutic efficacy in biliary fibrosis was tested in BALB/c.Mdr2−/− and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed mice. Collagen crosslinking, fibrosis progression and reversal were assessed histologically and biochemically. HPC differentiation was studied in primary EpCAM(+) liver cells in vitro.
Results
LOXL2 was virtually absent from healthy but strongly induced in fibrotic liver, with predominant localisation within fibrotic septa. Delayed anti-LOXL2 treatment of active TAA …
引用总数
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