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2016 ; 6
(ä): 133
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Lipopolysaccharide Induces Human Pulmonary Micro-Vascular Endothelial Apoptosis
via the YAP Signaling Pathway
#MMPMID27807512
Yi L
; Huang X
; Guo F
; Zhou Z
; Chang M
; Tang J
; Huan J
Front Cell Infect Microbiol
2016[]; 6
(ä): 133
PMID27807512
show ga
Gram-negative bacterial lipopolysaccharide (LPS) induces a pathologic increase in
lung vascular leakage under septic conditions. LPS-induced human pulmonary
micro-vascular endothelial cell (HPMEC) apoptosis launches and aggravates
micro-vascular hyper-permeability and acute lung injury (ALI). Previous studies
show that the activation of intrinsic apoptotic pathway is vital for LPS-induced
EC apoptosis. Yes-associated protein (YAP) has been reported to positively
regulate intrinsic apoptotic pathway in tumor cells apoptosis. However, the
potential role of YAP protein in LPS-induced HPMEC apoptosis has not been
determined. In this study, we found that LPS-induced activation and nuclear
accumulation of YAP accelerated HPMECs apoptosis. LPS-induced YAP translocation
from cytoplasm to nucleus by the increased phosphorylation on Y357 resulted in
the interaction between YAP and transcription factor P73. Furthermore, inhibition
of YAP by small interfering RNA (siRNA) not only suppressed the LPS-induced HPMEC
apoptosis but also regulated P73-mediated up-regulation of BAX and
down-regulation of BCL-2. Taken together, our results demonstrated that
activation of the YAP/P73/(BAX and BCL-2)/caspase-3 signaling pathway played a
critical role in LPS-induced HPMEC apoptosis. Inhibition of the YAP might be a
potential therapeutic strategy for lung injury under sepsis.
|*Apoptosis
[MESH]
|*Signal Transduction
[MESH]
|Adaptor Proteins, Signal Transducing/*metabolism
[MESH]