title: Mesenchymal stem cells in alleviating sepsis-induced mice cardiac dysfunction via inhibition of mTORC1-p70S6K signal pathway.
abstract: 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 vivobioluminescence 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 vitrocell 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.
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Shanxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Shanxi, China.
authors.forename: Wensi
authors.initials: W
authors.lastname: Fan
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital , Beijing, China.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Shanxi, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Shanxi, China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Shanxi, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University , Shanxi, China.
authors.forename: Congye
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital , Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Third Military Medical University , Chongqing, China.
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital , Beijing, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital , Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Cao