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@ARTICLE{Zhang:131010,
author = {W. Zhang and M. Freichel and F. van der Hoeven$^*$ and P.
P. Nawroth and H. Katus and F. Kälble and E. Zitron and V.
Schwenger},
title = {{N}ovel {E}ndothelial {C}ell-{S}pecific {AQP}1 {K}nockout
{M}ice {C}onfirm the {C}rucial {R}ole of {E}ndothelial
{AQP}1 in {U}ltrafiltration during {P}eritoneal {D}ialysis.},
journal = {PLoS one},
volume = {11},
number = {1},
issn = {1932-6203},
address = {Lawrence, Kan.},
publisher = {PLoS},
reportid = {DKFZ-2017-06086},
pages = {e0145513 -},
year = {2016},
abstract = {The water channel aquaporin-1 (AQP1) mediates about $50\%$
ultrafiltration during a 2-hour hypertonic dwell in global
AQP1 knockout (AQP1-/-) mice. Although AQP1 is widely
expressed in various cell types including mesothelial cells,
the ultrafiltration has been assumed to be mediated via
endothelial AQP1 of the peritoneum. The partial embryonic
lethality and reduced body weight in AQP1-/- mice may
reflect potential confounding phenotypic effects evoked by
ubiquitous AQP1 deletion, which may interfere with
functional analysis of endothelial AQP1. Using a Cre/loxP
approach, we generated and characterised endothelial cell-
and time-specific AQP1 knockout (AQP1fl/fl; Cdh5-Cre+) mice.
Compared to controls, AQP1fl/fl; Cdh5-Cre+ mice showed no
difference in an initial clinical and biological analysis at
baseline, including body weight and survival. During a
1-hour $3.86\%$ mini-peritoneal equilibration test
(mini-PET), AQP1fl/fl; Cdh5-Cre+ mice exhibited strongly
decreased indices for AQP1-related transcellular water
transport $(43.0\%$ in net ultrafiltration, $93.0\%$ in
sodium sieving and $57.9\%$ in free water transport)
compared to controls. The transport rates for small solutes
of urea and glucose were not significantly altered. Our data
provide the first direct experimental evidence for the
functional relevance of endothelial AQP1 to the fluid
transport in peritoneal dialysis and thereby further
validate essential predictions of the three-pore model of
peritoneal transport.},
keywords = {Water (NLM Chemicals) / Aquaporin 1 (NLM Chemicals)},
cin = {W450},
ddc = {500},
cid = {I:(DE-He78)W450-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26760974},
pmc = {pmc:PMC4711985},
doi = {10.1371/journal.pone.0145513},
url = {https://inrepo02.dkfz.de/record/131010},
}