PMID- 19490419
OWN - NLM
STAT- MEDLINE
DCOM- 20091020
LR  - 20151119
IS  - 1478-3231 (Electronic)
IS  - 1478-3223 (Linking)
VI  - 29
IP  - 8
DP  - 2009 Sep
TI  - Cross-species immunohistochemical investigation of the activation of the liver 
      progenitor cell niche in different types of liver disease.
PG  - 1241-52
LID - 10.1111/j.1478-3231.2009.02024.x [doi]
AB  - BACKGROUND: When hepatocyte replication during liver disease is insufficient for 
      regeneration, liver progenitor cells (LPCs) are activated. The cells and stroma 
      in the immediate environment of LPCs, together termed the LPC niche, are thought 
      to play an important role in this activation. Among these cells are the hepatic 
      stellate cells (HSCs)/myofibroblasts (MFs). AIMS/METHODS: We assessed the 
      activation of HSC/MFs and LPCs in relation to the histological location and 
      extent of liver disease in immunohistochemically (double) stained serial 
      sections. Markers of HSC/MFs [alpha-smooth muscle actin, glial fibrillary acidic 
      protein (GFAP), neurotrophin 3 and neural-cell adhesion molecule], markers of 
      LPCs (keratin 7 and keratin 19) and a proliferation marker (Ki67) were used. A 
      very relevant spontaneous model to evaluate LPC niche activation in a 
      translational approach seems to be the dog. Therefore, both human and canine 
      liver diseases with different degree of fibrosis and disease activity were 
      included. RESULTS: In human and canine liver disease, type and extent of LPC 
      niche activation depended on type and severity of disease (P<0.05) and 
      corresponded to the main location of disease. Activated HSCs surrounded the 
      activated LPCs. In chronic hepatitis and non-alcoholic steatohepatitis 
      lobular-type HSCs were activated, while during biliary disease portal/septal MFs 
      were mainly activated. In canine liver, GFAP further presented as an early marker 
      of HSC activation. Activation of the LPCs correlated with disease location and 
      severity (P<0.01), and was inversely related to hepatocyte proliferation, as was 
      previously shown in man. CONCLUSION: A shared involvement of HSC/MFs, LPCs and 
      disease severity during hepatic disease processes is shown, which is highly 
      similar in man and dog.
FAU - Schotanus, Baukje A
AU  - Schotanus BA
AD  - Department of Clinical Sciences of Companion Animals, Faculty of Veterinary 
      Medicine, Utrecht University, Utrecht, the Netherlands. b.a.schotanus@uu.nl
FAU - van den Ingh, Ted S G A M
AU  - van den Ingh TS
FAU - Penning, Louis C
AU  - Penning LC
FAU - Rothuizen, Jan
AU  - Rothuizen J
FAU - Roskams, Tania A
AU  - Roskams TA
FAU - Spee, Bart
AU  - Spee B
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20090420
PL  - United States
TA  - Liver Int
JT  - Liver international : official journal of the International Association for the 
      Study of the Liver
JID - 101160857
RN  - 0 (Biomarkers)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Dogs
MH  - Fluorescent Antibody Technique, Indirect/*methods
MH  - Hepatic Stellate Cells/metabolism/*pathology
MH  - Humans
MH  - Immunoenzyme Techniques/*methods
MH  - Liver/metabolism/*pathology
MH  - Liver Diseases/pathology/*veterinary
MH  - Species Specificity
EDAT- 2009/06/06 09:00
MHDA- 2009/10/21 06:00
CRDT- 2009/06/04 09:00
PHST- 2009/06/04 09:00 [entrez]
PHST- 2009/06/06 09:00 [pubmed]
PHST- 2009/10/21 06:00 [medline]
AID - LIV2024 [pii]
AID - 10.1111/j.1478-3231.2009.02024.x [doi]
PST - ppublish
SO  - Liver Int. 2009 Sep;29(8):1241-52. doi: 10.1111/j.1478-3231.2009.02024.x. Epub 
      2009 Apr 20.