PMID- 22946653
OWN - NLM
STAT- MEDLINE
DCOM- 20130404
LR  - 20211021
IS  - 1029-2292 (Electronic)
IS  - 0897-7194 (Print)
IS  - 0897-7194 (Linking)
VI  - 30
IP  - 5
DP  - 2012 Oct
TI  - Myofibroblast keratinocyte growth factor reduces tight junctional integrity and 
      increases claudin-2 levels in polarized Caco-2 cells.
PG  - 320-32
AB  - The colonic epithelium is composed of a polarized monolayer sheathed by a layer 
      of pericryptal myofibroblasts (PCMFs). We mimicked these cellular compartments in 
      vitro to assess the effects of paracrine-acting PCMF-derived factors on tight 
      junction (TJ) integrity, as measured by transepithelial electrical resistance 
      (TER). Coculture with 18Co PCMFs, or basolateral administration of 18Co 
      conditioned medium, significantly reduced TER of polarized Caco-2 cells. Among 
      candidate paracrine factors, only keratinocyte growth factor (KGF) reduced Caco-2 
      TER; basolateral KGF treatment led to time- and concentration-dependent increases 
      in claudin-2 levels. We also demonstrate that amphiregulin (AREG), produced 
      largely by Caco-2 cells, increased claudin-2 levels, leading to epidermal growth 
      factor receptor-mediated TER reduction. We propose that colonic epithelial TJ 
      integrity can be modulated by paracrine KGF and autocrine AREG through increased 
      claudin-2 levels. KGF-regulated claudin-2 induction may have implications for 
      inflammatory bowel disease, where both KGF and claudin-2 are upregulated.
FAU - Kim, Tae Il
AU  - Kim TI
AD  - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 
      37232, USA.
FAU - Poulin, Emily J
AU  - Poulin EJ
FAU - Blask, Elliot
AU  - Blask E
FAU - Bukhalid, Raghida
AU  - Bukhalid R
FAU - Whitehead, Robert H
AU  - Whitehead RH
FAU - Franklin, Jeffrey L
AU  - Franklin JL
FAU - Coffey, Robert J
AU  - Coffey RJ
LA  - eng
GR  - CA46413/CA/NCI NIH HHS/United States
GR  - P50 CA095103/CA/NCI NIH HHS/United States
GR  - R01 CA046413/CA/NCI NIH HHS/United States
GR  - P30 DK058404/DK/NIDDK NIH HHS/United States
GR  - R01 CA151566/CA/NCI NIH HHS/United States
GR  - EY08126/EY/NEI NIH HHS/United States
GR  - P30 EY008126/EY/NEI NIH HHS/United States
GR  - CA68485/CA/NCI NIH HHS/United States
GR  - HD15052/HD/NICHD NIH HHS/United States
GR  - DK20593/DK/NIDDK NIH HHS/United States
GR  - U24 DK059637/DK/NIDDK NIH HHS/United States
GR  - P60 DK020593/DK/NIDDK NIH HHS/United States
GR  - P50CA095103/CA/NCI NIH HHS/United States
GR  - T32GM008554/GM/NIGMS NIH HHS/United States
GR  - DK58404/DK/NIDDK NIH HHS/United States
GR  - P30 HD015052/HD/NICHD NIH HHS/United States
GR  - CA151566/CA/NCI NIH HHS/United States
GR  - DK59637/DK/NIDDK NIH HHS/United States
GR  - P30 DK020593/DK/NIDDK NIH HHS/United States
GR  - P30 CA068485/CA/NCI NIH HHS/United States
GR  - T32 GM008554/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120905
PL  - England
TA  - Growth Factors
JT  - Growth factors (Chur, Switzerland)
JID - 9000468
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Claudin-2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Ligands)
RN  - 126469-10-1 (Fibroblast Growth Factor 7)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Amphiregulin
MH  - Caco-2 Cells
MH  - Cell Communication
MH  - Cell Line, Tumor
MH  - Cell Membrane Permeability
MH  - Cell Proliferation
MH  - Claudin-2/*metabolism
MH  - Culture Media, Conditioned
MH  - EGF Family of Proteins
MH  - Electric Impedance
MH  - ErbB Receptors/metabolism
MH  - Fibroblast Growth Factor 7/*metabolism
MH  - Glycoproteins/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Intestinal Mucosa/metabolism/*physiology
MH  - Ligands
MH  - Myofibroblasts/*physiology
MH  - Tight Junctions/*physiology
PMC - PMC3594790
MID - NIHMS445143
COIS- Declaration of Interest The authors report no declarations of interest.
EDAT- 2012/09/06 06:00
MHDA- 2013/04/05 06:00
PMCR- 2013/10/01
CRDT- 2012/09/06 06:00
PHST- 2012/09/06 06:00 [entrez]
PHST- 2012/09/06 06:00 [pubmed]
PHST- 2013/04/05 06:00 [medline]
PHST- 2013/10/01 00:00 [pmc-release]
AID - 10.3109/08977194.2012.717076 [doi]
PST - ppublish
SO  - Growth Factors. 2012 Oct;30(5):320-32. doi: 10.3109/08977194.2012.717076. Epub 
      2012 Sep 5.