PMID- 16282363
OWN - NLM
STAT- MEDLINE
DCOM- 20060510
LR  - 20220227
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 290
IP  - 4
DP  - 2006 Apr
TI  - Secretion of MCP-1/CCL2 by bile duct epithelia induces myofibroblastic 
      transdifferentiation of portal fibroblasts.
PG  - G765-71
AB  - Portal fibroblasts (PF) are fibrogenic liver cells distinct from hepatic stellate 
      cells (HSC). Recent evidence suggests that PF may be important mediators of 
      biliary fibrosis and cirrhosis. The cytokine monocyte chemoattractant protein-1 
      (MCP-1)/CCL2 is upregulated in biliary fibrosis by bile duct epithelia (BDE) and 
      induces functional responses in HSC. Thus we hypothesized that release of MCP-1 
      may mediate biliary fibrosis. We report that PF express functional receptors for 
      MCP-1 that are distinct from the receptor CCR2. MCP-1 induces proliferation, 
      increase and redistribution of alpha-smooth muscle (alpha-SMA) expression, loss 
      of the ectonucleotidase NTPDase2, and upregulation of alpha(1)-procollagen 
      production in PF. BDE secretions induce alpha-SMA levels in PF, and this is 
      inhibited by MCP-1 blocking antibody. Together, these data suggest that BDE 
      regulate PF proliferation and myofibroblastic transdifferentiation in a paracrine 
      fashion via release of MCP-1.
FAU - Kruglov, Emma A
AU  - Kruglov EA
AD  - Section of Digestive Diseases and Yale Liver Center, Yale University School of 
      Medicine, New Haven, CT 06520, USA.
FAU - Nathanson, Rebecca A
AU  - Nathanson RA
FAU - Nguyen, Trong
AU  - Nguyen T
FAU - Dranoff, Jonathan A
AU  - Dranoff JA
LA  - eng
GR  - DK-02379/DK/NIDDK NIH HHS/United States
GR  - DK-066287/DK/NIDDK NIH HHS/United States
GR  - DK-45710/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20051110
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
SB  - IM
MH  - Animals
MH  - Bile Ducts/*metabolism
MH  - Cell Differentiation/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/*administration & dosage/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Epithelium/*metabolism
MH  - Fibroblasts/*cytology/*drug effects/metabolism
MH  - Liver/*cytology/*drug effects/metabolism
MH  - Male
MH  - Myocytes, Smooth Muscle/cytology/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2005/11/12 09:00
MHDA- 2006/05/11 09:00
CRDT- 2005/11/12 09:00
PHST- 2005/11/12 09:00 [pubmed]
PHST- 2006/05/11 09:00 [medline]
PHST- 2005/11/12 09:00 [entrez]
AID - 00308.2005 [pii]
AID - 10.1152/ajpgi.00308.2005 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2006 Apr;290(4):G765-71. doi: 
      10.1152/ajpgi.00308.2005. Epub 2005 Nov 10.