Tri-iodothyronine preconditioning protects against liver ischemia reperfusion injury through the regulation of autophagy by the MEK/ERK/mTORC1 axis.
OBJECTIVE
The autophagy pathway has previously been suggested as an important protective factor in liver injury. The purpose of this study is to demonstrate the protective, autophagy-modulating effect of tri-iodothyronine (T3) on liver ischemia reperfusion injury.


METHODS
Liver ischemia reperfusion was induced in male C57BL/6 mice after T3 administration. Liver function, histological damage, inflammatory infiltration, cytokine production, oxidative stress, antioxidant capacity, autophagy changing, and autophagy-associated intracellular signaling pathway were assessed to evaluate the impact of antecedent T3 treatment on ischemia reperfusion induced liver injury.


RESULTS
After 70% liver ischemia reperfusion injury, mice that were preconditioned with appropriate T3 displayed significantly preserved liver function, less histological damage, less apoptosis, and enhanced antioxidant capacity. Further studies revealed that mice which were preconditioned with T3 before IR induction exhibited an increased level of autophagy mediated by MEK/ERK/mTORC1.


CONCLUSIONS
Our results provide the first line of evidence indicating that antecedent T3 injection can provide protection for the liver against ischemia reperfusion induced injury by enhancing autophagy. Therefore, T3 preconditioning could be a potential therapeutic approach to prevent liver IR injury related to various clinical conditions.
Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai, China.
Jinghui
J
Yang
Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai, China.
Yang
Y
Wang
Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai, China.
Mingxing
M
Sui
Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai, China.
Fang
F
Liu
Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai, China. Electronic address: zhirenf@sh163.net.
Zhiren
Z
Fu
National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, China. Electronic address: wangqx@immunol.org.
Quan-Xing
QX
Wang
D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000378:metabolism*; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000517:prevention & control*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014284:Triiodothyronine / Q000008:administration & dosage*
D046912:Multiprotein Complexes; D014284:Triiodothyronine; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases
3,3,5-Triiodothyronine; Autophagy; Liver ischemia reperfusion