PMID- 32483425
OWN - NLM
STAT- MEDLINE
DCOM- 20210802
LR  - 20231213
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 10
IP  - 13
DP  - 2020
TI  - Interleukin-22 drives a metabolic adaptive reprogramming to maintain 
      mitochondrial fitness and treat liver injury.
PG  - 5879-5894
LID - 10.7150/thno.43894 [doi]
AB  - Rationale: Interleukin 22 (IL-22) is an epithelial survival cytokine that is at 
      present being explored as therapeutic agents for acute and chronic liver injury. 
      However, its molecular basis of protective activities remains poorly understood. 
      Methods: Here we demonstrate that IL-22 inhibits the deteriorating metabolic 
      states induced by stimuli in hepatocytes. Utilizing cell biological, molecular, 
      and biochemical approaches, we provide evidence that IL-22 promotes oxidative 
      phosphorylation (OXPHOS) and glycolysis and regulates the metabolic reprogramming 
      related transcriptional responses. Results: IL-22 controls metabolic regulators 
      and enzymes activity through the induction of AMP-activated protein kinase 
      (AMPK), AKT and mammalian target of rapamycin (mTOR), thereby ameliorating 
      mitochondrial dysfunction. The upstream effector lncRNA H19 also participates in 
      the controlling of these metabolic processes in hepatocytes. Importantly, 
      amelioration of liver injury by IL-22 through activation of metabolism relevant 
      signaling and regulation of mitochondrial function are further demonstrated in 
      cisplatin-induced liver injury and steatohepatitis. Conclusions: Collectively, 
      our results reveal a novel mechanism underscoring the regulation of metabolic 
      profiles of hepatocytes by IL-22 during liver injury, which might provide useful 
      insights from the bench to the clinic in treating and preventing liver diseases.
CI  - (c) The author(s).
FAU - Chen, Wei
AU  - Chen W
AD  - Minhang Hospital & Shanghai Engineering Research Center of Immunotherapeutics, 
      School of Pharmacy, Fudan University, Shanghai, China.
AD  - Department of Ophthalmology, Stanford University School of Medicine, Palo Alto CA 
      94304, USA.
FAU - Zai, Wenjing
AU  - Zai W
AD  - Minhang Hospital & Shanghai Engineering Research Center of Immunotherapeutics, 
      School of Pharmacy, Fudan University, Shanghai, China.
AD  - Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, 
      Shanghai Medical College of Fudan University.
FAU - Fan, Jiajun
AU  - Fan J
AD  - Minhang Hospital & Shanghai Engineering Research Center of Immunotherapeutics, 
      School of Pharmacy, Fudan University, Shanghai, China.
FAU - Zhang, Xuyao
AU  - Zhang X
AD  - Minhang Hospital & Shanghai Engineering Research Center of Immunotherapeutics, 
      School of Pharmacy, Fudan University, Shanghai, China.
FAU - Zeng, Xian
AU  - Zeng X
AD  - Minhang Hospital & Shanghai Engineering Research Center of Immunotherapeutics, 
      School of Pharmacy, Fudan University, Shanghai, China.
FAU - Luan, Jingyun
AU  - Luan J
AD  - Minhang Hospital & Shanghai Engineering Research Center of Immunotherapeutics, 
      School of Pharmacy, Fudan University, Shanghai, China.
FAU - Wang, Yichen
AU  - Wang Y
AD  - Minhang Hospital & Shanghai Engineering Research Center of Immunotherapeutics, 
      School of Pharmacy, Fudan University, Shanghai, China.
FAU - Shen, Yilan
AU  - Shen Y
AD  - Department of Nephrology, Changhai Hospital, Second Military Medical University, 
      Shanghai, China.
FAU - Wang, Ziyu
AU  - Wang Z
AD  - Department of Pharmacy, Huadong Hospital, Fudan University, Shanghai, China.
FAU - Dai, Shixuan
AU  - Dai S
AD  - Minhang Hospital & Shanghai Engineering Research Center of Immunotherapeutics, 
      School of Pharmacy, Fudan University, Shanghai, China.
FAU - Fang, Si
AU  - Fang S
AD  - Minhang Hospital & Shanghai Engineering Research Center of Immunotherapeutics, 
      School of Pharmacy, Fudan University, Shanghai, China.
AD  - Tongcheng Hospital of Traditional Chinese Medicine, Anhui 231400, P. R. China.
FAU - Zhao, Zhen
AU  - Zhao Z
AD  - Minhang Hospital & Shanghai Engineering Research Center of Immunotherapeutics, 
      School of Pharmacy, Fudan University, Shanghai, China.
FAU - Ju, Dianwen
AU  - Ju D
AD  - Minhang Hospital & Shanghai Engineering Research Center of Immunotherapeutics, 
      School of Pharmacy, Fudan University, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200427
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (Interleukins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
CIN - Theranostics. 2020 Jun 19;10(17):7836-7840. PMID: 32685023
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Apoptosis/physiology
MH  - Chemical and Drug Induced Liver Injury/immunology/*metabolism
MH  - Glycolysis/physiology
MH  - Hepatocytes/immunology/*metabolism
MH  - Interleukins/*metabolism/physiology
MH  - Liver/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria/metabolism
MH  - Oxidative Phosphorylation
MH  - Oxidative Stress/physiology
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Interleukin-22
PMC - PMC7254999
OTO - NOTNLM
OT  - glycolysis
OT  - lncRNA H19
OT  - mitochondria
OT  - oxidative phosphorylation
OT  - reactive oxygen species
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2020/06/03 06:00
MHDA- 2021/08/03 06:00
PMCR- 2020/01/01
CRDT- 2020/06/03 06:00
PHST- 2020/01/13 00:00 [received]
PHST- 2020/04/15 00:00 [accepted]
PHST- 2020/06/03 06:00 [entrez]
PHST- 2020/06/03 06:00 [pubmed]
PHST- 2021/08/03 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - thnov10p5879 [pii]
AID - 10.7150/thno.43894 [doi]
PST - epublish
SO  - Theranostics. 2020 Apr 27;10(13):5879-5894. doi: 10.7150/thno.43894. eCollection 
      2020.