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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Pediatr+Res
2017 ; 82
(5
): 855-862
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Foxd1 is an upstream regulator of the renin-angiotensin system during metanephric
kidney development
#MMPMID28665931
Song R
; Lopez MLSS
; Yosypiv IV
Pediatr Res
2017[Nov]; 82
(5
): 855-862
PMID28665931
show ga
BackgroundWe tested the hypothesis that Foxd1, a transcription factor essential
for normal kidney development, is an upstream regulator of the renin-angiotensin
system (RAS) during ureteric bud (UB)-branching morphogenesis.MethodsUB
branching, RAS gene, and protein expression were studied in embryonic mouse
kidneys. RAS mRNA expression was studied in mesenchymal MK4 cells.ResultsThe
number of UB tips was reduced in Foxd1(-/-) compared with that in Foxd1(+/+)
metanephroi on embryonic day E12.5 (14±2.1 vs. 28±1.3, P<0.05). Quantitative
real-time reverse-transcription polymerase chain reaction (qRT-PCR) demonstrated
that renin, angiotensin I-converting enzyme (ACE), and angiotensin (Ang) II
receptor type 1 (AT(1)R) mRNA levels were decreased in Foxd1(-/-) compared with
those in Foxd1(+/+) E14.5 metanephroi. Western blot analysis and
immunohistochemistry showed decreased expression of AGT and renin proteins in
Foxd1(-/-) metanephroi compared with that in Foxd1(+/+) metanephroi. Foxd1
overexpression in mesenchymal MK4 cells in vitro increased renin, AGT, ACE, and
AT(1)R mRNA levels. Exogenous Ang II stimulated UB branching equally in whole
intact E12.5 Foxd1(-/-) and Foxd1(+/+) metanephroi grown ex vivo (+364±21% vs.
+336±18%, P=0.42).ConclusionWe conclude that Foxd1 is an upstream positive
regulator of RAS during early metanephric development and propose that the
cross-talk between Foxd1 and RAS is essential in UB-branching morphogenesis.