title: The role of 1,25-dyhydroxyvitamin D3 in mouse liver ischemia reperfusion injury: regulation of autophagy through activation of MEK/ERK signaling and PTEN/PI3K/Akt/mTORC1 signaling.
abstract: Autophagy is an important mechanism for cellular homeostasis and survival during pathologic stress conditions in the liver, such as ischemia-reperfusion injury. In this study, we hypothesized a protective role of vitamin Din hepatic IR model. The administration of vitamin D displayed significantly preserved liver function as characterized by less histological damage and reduced serum enzymes level. We found that the protective effect was associated with ameliorated oxidative stress as manifested by the increase of antioxidant capacity and decrease of lipid peroxidation. Further, increased autophagic flux after vitamin D administration was demonstrated by the increase of protein light chain 3 (LC3) conversion both in vivo and in vitro. MEK/ERK and PTEN/PI3K/Akt/mTOR were both found critically involved in vitamin D-induced autophagy. By employing intracellular ROS and cell viability assay, we further confirmed this hypothesis with the observation that inhibition either of the MEK/ERK or PTEN/PI3K/Akt/mTOR pathway partly abolished the protective effect of vitamin D-induced autophagy, while inhibiting initiation of autophagy signaling pathway by knockdown of Beclin-1 completely reversed the protection provided by vitamin D. Collectively, the present results indicate that the protective role of vitamin D in murine hepatic IR injury is autophagy dependent, which is regulated by both MEK/ERK and PTEN/PI3K/Akt/mTOR pathway.
authors.affiliation: Department of Organ Transplantation, Shanghai Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Health Statistics, Second Military Medical University Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Health Statistics, Second Military Medical University Shanghai, China.
authors.forename: Shiyin
authors.initials: S
authors.lastname: Tian
authors.affiliation: Department of Organ Transplantation, Shanghai Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Organ Transplantation, Shanghai Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Medical Immunology, Second Military Medical University Shanghai, China.
authors.forename: Quanxing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Organ Transplantation, Shanghai Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Fu
keywords: Ischemia reperfusion injury; autophagy; vitamin D