PMID- 17574589
OWN - NLM
STAT- MEDLINE
DCOM- 20070830
LR  - 20220311
IS  - 0022-4804 (Print)
IS  - 1095-8673 (Electronic)
IS  - 0022-4804 (Linking)
VI  - 141
IP  - 2
DP  - 2007 Aug
TI  - Paclitaxel interrupts TGF-beta1 signaling between gallbladder epithelial cells 
      and myofibroblasts.
PG  - 183-91
AB  - BACKGROUND: The cellular and molecular mechanisms of fibrogenesis in the 
      extrahepatic biliary epithelium are not known. Transforming growth factor-beta1 
      (TGF-beta1) is a cytokine implicated in signaling pathways that mediate collagen 
      formation. An observation that paclitaxel (PT), applied topically into the rat 
      common bile duct, inhibited stricture formation led us to hypothesize that PT's 
      effects might be due to interruption of TGF-beta1 signaling between biliary 
      epithelial cells and subepithelial myofibroblasts. MATERIALS AND METHODS: We 
      tested this hypothesis using an in vitro cell-culture model in which murine 
      gallbladder epithelial cells (GBEC) are cultured separately or cocultured with 
      human gallbladder myofibroblasts (GBMF). RESULTS: Exposure to Escherichia coli 
      lipopolysaccharide (LPS) enhanced TGF-beta1 mRNA expression and stimulated 
      TGF-beta1 protein secretion into both apical and basolateral compartments in 
      GBEC. This effect was more prominent with basolateral secretion and was also more 
      pronounced in the coculture system. In GBMF, collagen I mRNA expression and 
      protein secretion were stimulated by treatment with LPS or TGF-beta1. GBMF also 
      expressed TGF-beta1 mRNA, whose levels were enhanced by exposure to either LPS or 
      exogenous TGF-beta1. PT inhibited LPS-induced TGF-beta1 mRNA expression and 
      protein secretion in GBEC in both culture systems. Tumor necrosis factor-alpha 
      mRNA expression and protein secretion were not affected by PT in GBEC, 
      demonstrating that the effects were specific for TGF-beta1. PT also inhibited 
      LPS- and TGF-beta1-induced collagen I mRNA expression and protein secretion in 
      GBMF. CONCLUSIONS: These findings support a model in which GBEC communicate with 
      subepithelial GBMF via TGF-beta1, leading to collagen deposition and fibrosis, 
      and in which GBMF possess autocrine mechanisms involving TGF-beta1 that could 
      regulate collagen production. PT inhibits these fibrogenic pathways.
FAU - Choi, Ho-Soon
AU  - Choi HS
AD  - Division of Gastroenterology, Department of Medicine, University of Washington, 
      Seattle, Washington. 98195, USA.
FAU - Savard, Christopher E
AU  - Savard CE
FAU - Choi, Jae-Woon
AU  - Choi JW
FAU - Kuver, Rahul
AU  - Kuver R
FAU - Lee, Sum P
AU  - Lee SP
LA  - eng
GR  - R01 DK050246/DK/NIDDK NIH HHS/United States
GR  - R01 DK050246-04/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070614
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Collagen Type I)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Animals
MH  - Cell Communication/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Collagen Type I/genetics
MH  - Epithelial Cells/*physiology
MH  - Fibroblasts/*physiology
MH  - Fibrosis
MH  - Gallbladder/*pathology
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Paclitaxel/*pharmacology
MH  - RNA, Messenger/analysis
MH  - Signal Transduction/*drug effects
MH  - Transforming Growth Factor beta1/genetics/*physiology
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC3571727
MID - NIHMS27613
EDAT- 2007/06/19 09:00
MHDA- 2007/08/31 09:00
PMCR- 2013/02/13
CRDT- 2007/06/19 09:00
PHST- 2006/05/17 00:00 [received]
PHST- 2006/12/13 00:00 [revised]
PHST- 2006/12/21 00:00 [accepted]
PHST- 2007/06/19 09:00 [pubmed]
PHST- 2007/08/31 09:00 [medline]
PHST- 2007/06/19 09:00 [entrez]
PHST- 2013/02/13 00:00 [pmc-release]
AID - S0022-4804(06)01183-8 [pii]
AID - 10.1016/j.jss.2006.12.558 [doi]
PST - ppublish
SO  - J Surg Res. 2007 Aug;141(2):183-91. doi: 10.1016/j.jss.2006.12.558. Epub 2007 Jun 
      14.