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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 J+Am+Heart+Assoc
2016 ; 5
(2
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
miR-342-5p Is a Notch Downstream Molecule and Regulates Multiple Angiogenic
Pathways Including Notch, Vascular Endothelial Growth Factor and Transforming
Growth Factor ? Signaling
#MMPMID26857067
Yan XC
; Cao J
; Liang L
; Wang L
; Gao F
; Yang ZY
; Duan JL
; Chang TF
; Deng SM
; Liu Y
; Dou GR
; Zhang J
; Zheng QJ
; Zhang P
; Han H
J Am Heart Assoc
2016[Feb]; 5
(2
): ä PMID26857067
show ga
BACKGROUND: Endothelial cells (ECs) form blood vessels through angiogenesis that
is regulated by coordination of vascular endothelial growth factor (VEGF), Notch,
transforming growth factor ?, and other signals, but the detailed molecular
mechanisms remain unclear. METHODS AND RESULTS: Small RNA sequencing initially
identified miR-342-5p as a novel downstream molecule of Notch signaling in ECs.
Reporter assay, quantitative reverse transcription polymerase chain reaction and
Western blot analysis indicated that miR-342-5p targeted endoglin and modulated
transforming growth factor ? signaling by repressing SMAD1/5 phosphorylation in
ECs. Transfection of miR-342-5p inhibited EC proliferation and lumen formation
and reduced angiogenesis in vitro and in vivo, as assayed by using a fibrin
beads-based sprouting assay, mouse aortic ring culture, and intravitreal
injection of miR-342-5p agomir in P3 pups. Moreover, miR-342-5p promoted the
migration of ECs, accompanied by reduced endothelial markers and increased
mesenchymal markers, indicative of increased endothelial-mesenchymal transition.
Transfection of endoglin at least partially reversed endothelial-mesenchymal
transition induced by miR-342-5p. The expression of miR-342-5p was upregulated by
transforming growth factor ?, and inhibition of miR-342-5p attenuated the
inhibitory effects of transforming growth factor ? on lumen formation and
sprouting by ECs. In addition, VEGF repressed miR-342-5p expression, and
transfection of miR-342-5p repressed VEGFR2 and VEGFR3 expression and
VEGF-triggered Akt phosphorylation in ECs. miR-342-5p repressed angiogenesis in a
laser-induced choroidal neovascularization model in mice, highlighting its
clinical potential. CONCLUSIONS: miR-342-5p acts as a multifunctional angiogenic
repressor mediating the effects and interaction among angiogenic pathways.