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2017 ; 3
(ä): 16097
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Mesenchymal stem cells in alleviating sepsis-induced mice cardiac dysfunction via
inhibition of mTORC1-p70S6K signal pathway
#MMPMID28250969
Huang W
; Fan W
; Wang Y
; Han D
; Li X
; Li S
; Li C
; Xu B
; Huang Y
; Fu X
; Cao F
Cell Death Discov
2017[]; 3
(ä): 16097
PMID28250969
show ga
Sepsis-induced cardiac dysfunction remains a major cause of morbidity and
mortality in patients suffered from severe trauma. Mesenchymal stem cells (MSCs)
-based treatment has been verified as a promising approach to mitigate the
sepsis-induced cardiac dysfunction, but the mechanism is still ambiguous. Thus,
our study was designed to explore the potential role of MSCs in sepsis-induced
cardiac dysfunction. In vivo bioluminescence imaging revealed 80% acute donor
cell death of bone marrow-derived MSCs (BM-MSCs) within 3 days after
transplantation. However, echocardiography demonstrated that systolic function in
wild-type mice group were reduced after sepsis, while the cardiac function was
relatively well persevered in cardiac-conditional deletion of Raptor (component
of mTORC1 complex) mice group. Raptor KO group treated with BM-MSCs appeared
better cardiac function than other groups (P<0.05). In vitro cell study revealed
that co-culture of H9C2 (Raptor-Knock down) and BM-MSC could attenuate the level
of proinflammatory cytokines and promote the expression of anti-inflammatory
cytokine accompanied by mTORC2-Akt activation (P<0.05). In contrast, co-culture
H9C2 (Raptor-O.E) and BM-MSC could aggravate the inflammatory response
accompanied by the activation of mTORC1-p70S6K and inhibition of mTORC2-Akt
(P<0.05). The immunomodulatory property of MSC is related to the inhibition of
mTORC1-p70S6K and activation of mTORC2-Akt signaling pathway. mTORC1-p70S6K and
mTORC2-Akt pathways were involved in the therapeutic adjuncts of MSC. The
possible mechanism due to MSC`s immunomodulatory property through activation of
mTORC2-Akt and inhibition of mTORC1-p70S6K signal pathways which may lead to
modulate the expression of inflammation cytokines.