PMID- 19296469
OWN - NLM
STAT- MEDLINE
DCOM- 20090602
LR  - 20220330
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 49
IP  - 5
DP  - 2009 May
TI  - Relation between liver progenitor cell expansion and extracellular matrix 
      deposition in a CDE-induced murine model of chronic liver injury.
PG  - 1625-35
LID - 10.1002/hep.22820 [doi]
AB  - In chronic liver injury, liver progenitor cells (LPCs) proliferate in the 
      periportal area, migrate inside the lobule, and undergo further differentiation. 
      This process is associated with extracellular matrix (ECM) remodeling. We 
      analyzed LPC expansion and matrix accumulation in a choline-deficient, 
      ethionine-supplemented (CDE) model of LPC proliferation. After day 3, CDE induced 
      collagen deposits in the periportal area. Expansion of LPCs as assessed by 
      increased number of cytokeratin 19 (CK19)-positive cells was first observed at 
      day 7, while ECM accumulated 10 times more than in controls. Thereafter, LPCs and 
      ECM increased in parallel. Furthermore, ECM not only accumulates prior to the 
      increase in number of LPCs, but is also found in front of LPCs along the 
      porto-venous gradient of lobular invasion. Double immunostaining revealed that 
      LPCs are embedded in ECM at all times. Moreover, LPCs infiltrating the liver 
      parenchyma are chaperoned by alpha-smooth muscle actin (alpha-SMA)-positive 
      cells. Gene expression analyses confirmed these observations. The expression of 
      CK19, alpha-fetoprotein, E-cadherin, and CD49f messenger RNA (mRNA), largely 
      overexpressed by LPCs, significantly increased between day 7 and day 10. By 
      contrast, at day 3 there was a rapid burst in the expression of components of the 
      ECM, collagen I and laminin, as well as in alpha-SMA and connective tissue growth 
      factor expression. CONCLUSION: Our data demonstrate that, in a CDE model, ECM 
      deposition and activation of matrix-producing cells occurred as an initial phase, 
      prior to LPC expansion, and in front of LPCs along the porto-venous gradient of 
      lobular invasion. Those observations may reveal a fundamental role for the 
      established hepatic microenvironment or niche during the process of activation 
      and differentiation of liver progenitor cells.
FAU - Van Hul, Noemi K M
AU  - Van Hul NK
AD  - Laboratory of Gastroenterology, Faculty of Medicine, Universite Catholique de 
      Louvain, Brussels, Belgium.
FAU - Abarca-Quinones, Jorge
AU  - Abarca-Quinones J
FAU - Sempoux, Christine
AU  - Sempoux C
FAU - Horsmans, Yves
AU  - Horsmans Y
FAU - Leclercq, Isabelle A
AU  - Leclercq IA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - WX1BN24WZT (Ethionine)
SB  - IM
CIN - Hepatology. 2009 May;49(5):1424-6. PMID: 19399908
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Choline Deficiency/complications
MH  - Disease Models, Animal
MH  - Ethionine/toxicity
MH  - Extracellular Matrix/*metabolism
MH  - Gene Expression Profiling
MH  - Hepatic Stellate Cells/*physiology
MH  - Liver/*cytology/metabolism
MH  - Liver Diseases/etiology
MH  - *Liver Regeneration
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Time Factors
EDAT- 2009/03/20 09:00
MHDA- 2009/06/03 09:00
CRDT- 2009/03/20 09:00
PHST- 2009/03/20 09:00 [entrez]
PHST- 2009/03/20 09:00 [pubmed]
PHST- 2009/06/03 09:00 [medline]
AID - 10.1002/hep.22820 [doi]
PST - ppublish
SO  - Hepatology. 2009 May;49(5):1625-35. doi: 10.1002/hep.22820.