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Overexpression of Heparin-Binding Epidermal Growth Factor-Like Growth Factor Mediates Liver Fibrosis in Transgenic Mice.

Abstract The role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in liver fibrosis is not clear and is sometimes even contradictory. To clarify this role, a HB-EGF transgenic (Tg) mouse model was, for the first time, used to evaluate the functions of HB-EGF in liver fibrosis.
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Authors

Mayor MeshTerms

Gene Expression Regulation, Neoplastic

Keywords

Heparin-binding epidermal growth factor-like growth factor

Hepatic satellite cells

Liver fibrosis

Transgenic mice

Journal Title the american journal of the medical sciences
Publication Year Start




PMID- 28864379
OWN - NLM
STAT- MEDLINE
DA  - 20170902
DCOM- 20170908
LR  - 20170908
IS  - 1538-2990 (Electronic)
IS  - 0002-9629 (Linking)
VI  - 354
IP  - 2
DP  - 2017 Aug
TI  - Overexpression of Heparin-Binding Epidermal Growth Factor-Like Growth Factor
      Mediates Liver Fibrosis in Transgenic Mice.
PG  - 199-210
LID - S0002-9629(17)30221-5 [pii]
LID - 10.1016/j.amjms.2017.04.011 [doi]
AB  - BACKGROUND: The role of heparin-binding epidermal growth factor-like growth
      factor (HB-EGF) in liver fibrosis is not clear and is sometimes even
      contradictory. To clarify this role, a HB-EGF transgenic (Tg) mouse model was,
      for the first time, used to evaluate the functions of HB-EGF in liver fibrosis.
      MATERIALS AND METHODS: For the in vivo study, carbon tetrachloride injection and 
      bile duct ligation treatment were used to induce liver fibrosis in HB-EGF Tg mice
      and wild-type (WT) mice, respectively. Primary hepatic satellite cells (HSCs)
      were isolated from HB-EGF Tg and WT mice for the in vitro study. RESULTS:
      Compared with the WT mice, HB-EGF Tg mice were shown to develop more severe liver
      fibrosis when treated with carbon tetrachloride or bile duct ligation, with
      increased matrix metalloproteinases 13 activity and enhanced expression of
      fibrogenic genes including alpha-smooth muscle actin and collagen I. HB-EGF gene 
      transfer led to an increase in proliferation and a decrease in apoptosis in
      primary HSCs. The ERK signaling pathway was more highly activated in primary HSCs
      from HB-EGF Tg mice than in those from WT mice. CONCLUSIONS: Our investigation
      confirmed the profibrotic effect of HB-EGF on the liver using a Tg mouse model.
      This result may contribute to the elucidation of HB-EGF as a therapeutic target
      in liver fibrosis.
CI  - Copyright (c) 2017 Southern Society for Clinical Investigation. Published by
      Elsevier Inc. All rights reserved.
FAU - Guo, Yongze
AU  - Guo Y
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology,
      Shijiazhuang, Hebei, China.
FAU - Ding, Qian
AU  - Ding Q
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology,
      Shijiazhuang, Hebei, China.
FAU - Chen, Lei
AU  - Chen L
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology,
      Shijiazhuang, Hebei, China.
FAU - Ji, Chenguang
AU  - Ji C
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology,
      Shijiazhuang, Hebei, China.
FAU - Hao, Huiyao
AU  - Hao H
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology,
      Shijiazhuang, Hebei, China.
FAU - Wang, Jia
AU  - Wang J
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology,
      Shijiazhuang, Hebei, China.
FAU - Qi, Wei
AU  - Qi W
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology,
      Shijiazhuang, Hebei, China.
FAU - Xie, Xiaoli
AU  - Xie X
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology,
      Shijiazhuang, Hebei, China.
FAU - Ma, Junji
AU  - Ma J
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology,
      Shijiazhuang, Hebei, China.
FAU - Li, Aidi
AU  - Li A
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology,
      Shijiazhuang, Hebei, China.
FAU - Jiang, Xiaoyu
AU  - Jiang X
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology,
      Shijiazhuang, Hebei, China.
FAU - Li, Xiaotian
AU  - Li X
AD  - Department of Gastroenterology, The Affiliated Hospital of Hebei University of
      Engineering, Handan, Hebei, China.
FAU - Jiang, Huiqing
AU  - Jiang H
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology,
      Shijiazhuang, Hebei, China. Electronic address: [email protected]
LA  - eng
PT  - Journal Article
DEP - 20170420
PL  - United States
TA  - Am J Med Sci
JT  - The American journal of the medical sciences
JID - 0370506
RN  - 0 (Hbegf protein, mouse)
RN  - 0 (Heparin-binding EGF-like Growth Factor)
RN  - 9007-34-5 (Collagen)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Carbon Tetrachloride/toxicity
MH  - Collagen/*metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Heparin-binding EGF-like Growth Factor/*genetics/metabolism
MH  - Liver Cirrhosis/chemically induced/*genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
OTO - NOTNLM
OT  - Heparin-binding epidermal growth factor-like growth factor
OT  - Hepatic satellite cells
OT  - Liver fibrosis
OT  - Transgenic mice
EDAT- 2017/09/03 06:00
MHDA- 2017/09/09 06:00
CRDT- 2017/09/03 06:00
PHST- 2016/09/18 [received]
PHST- 2017/03/15 [revised]
PHST- 2017/04/17 [accepted]
AID - S0002-9629(17)30221-5 [pii]
AID - 10.1016/j.amjms.2017.04.011 [doi]
PST - ppublish
SO  - Am J Med Sci. 2017 Aug;354(2):199-210. doi: 10.1016/j.amjms.2017.04.011. Epub
      2017 Apr 20.