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KGF prevents hyperoxia-induced reduction of active ion transport in alveolar epithelial cells
Ist Teil von
American Journal of Physiology: Cell Physiology, 1999-06, Vol.276 (6), p.C1352-C1360
Ort / Verlag
United States
Erscheinungsjahr
1999
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Will Rogers Institute Pulmonary Research Center, Division of
Pulmonary and Critical Care Medicine, University of Southern
California, Los Angeles, California 90033
We evaluated the
effects of acute hyperoxic exposure on alveolar epithelial cell (AEC)
active ion transport and on expression of
Na + pump
(Na + -K + -ATPase)
and rat epithelial Na + channel
subunits. Rat AEC were cultivated in minimal defined serum-free medium
(MDSF) on polycarbonate filters. Beginning on day
5 , confluent monolayers were exposed
to either 95% air-5% CO 2
(normoxia) or 95% O 2 -5%
CO 2 (hyperoxia) for 48 h.
Transepithelial resistance
( R t ) and
short-circuit current
( I sc ) were
determined before and after exposure.
Na + channel -, -, and
-subunit and
Na + -K + -ATPase
1 - and
1 -subunit mRNA levels were
quantified by Northern analysis.
Na + pump
1 - and
1 -subunit protein abundance was
quantified by Western blotting. After hyperoxic exposure,
I sc across AEC
monolayers decreased by ~60% at 48 h relative to monolayers
maintained under normoxic conditions.
Na + channel -subunit mRNA
expression was reduced by hyperoxia, whereas - and -subunit mRNA
expression was unchanged. Na + pump
1 -subunit mRNA was unchanged,
whereas 1 -subunit mRNA was decreased ~80% by hyperoxia in parallel with a reduction in
1 -subunit protein. Because
keratinocyte growth factor (KGF) has recently been shown to upregulate
AEC active ion transport and expression of
Na + -K + -ATPase
under normoxic conditions, we assessed the ability of KGF to prevent
hyperoxia-induced changes in active ion transport by supplementing
medium with KGF (10 ng/ml) from day
2 . The presence of KGF prevented the
effects of hyperoxia on ion transport (as measured by
I sc ) relative
to normoxic controls. Levels of
1 mRNA and protein were
relatively preserved in monolayers maintained in MDSF and KGF compared
with those cultivated in MDSF alone. These results indicate that AEC
net active ion transport is decreased after 48 h of hyperoxia, likely
as a result of a decrease in the number of functional
Na + pumps per cell. KGF largely
prevents this decrease in active ion transport, at least in part, by
preserving Na + pump expression.
alveolar epithelium; growth factor; keratinocyte growth factor; oxygen toxicity; sodium transport