Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Theranostics 2020; 10(13):5879-5894. doi:10.7150/thno.43894 This issue Cite

Research Paper

Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury

Wei Chen1,2,#, Wenjing Zai1,3,#, Jiajun Fan1, Xuyao Zhang1, Xian Zeng1, Jingyun Luan1, Yichen Wang1, Yilan Shen4, Ziyu Wang5, Shixuan Dai1, Si Fang1,6, Zhen Zhao1✉, Dianwen Ju1✉

1. Minhang Hospital & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai, China
2. Department of Ophthalmology, Stanford University School of Medicine, Palo Alto CA 94304, USA
3. Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University
4. Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai, China
5. Department of Pharmacy, Huadong Hospital, Fudan University, Shanghai, China
6. Tongcheng Hospital of Traditional Chinese Medicine, Anhui 231400, P. R. China
#These authors contributed equally to this work.

✉ Corresponding author: Prof. Zhen Zhao, Email: fdmh_zzedu.cn. Prof. Dianwen Ju, E-mail: dianwenjuedu.cn. Minhang Hospital & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai, More

Citation:
Chen W, Zai W, Fan J, Zhang X, Zeng X, Luan J, Wang Y, Shen Y, Wang Z, Dai S, Fang S, Zhao Z, Ju D. Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury. Theranostics 2020; 10(13):5879-5894. doi:10.7150/thno.43894. https://www.thno.org/v10p5879.htm
Other styles

File import instruction

Abstract

Graphic abstract

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.

Keywords: oxidative phosphorylation, glycolysis, mitochondria, reactive oxygen species, lncRNA H19

Citation styles

APA
Chen, W., Zai, W., Fan, J., Zhang, X., Zeng, X., Luan, J., Wang, Y., Shen, Y., Wang, Z., Dai, S., Fang, S., Zhao, Z., Ju, D. (2020). Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury. Theranostics, 10(13), 5879-5894. https://doi.org/10.7150/thno.43894.

ACS
Chen, W.; Zai, W.; Fan, J.; Zhang, X.; Zeng, X.; Luan, J.; Wang, Y.; Shen, Y.; Wang, Z.; Dai, S.; Fang, S.; Zhao, Z.; Ju, D. Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury. Theranostics 2020, 10 (13), 5879-5894. DOI: 10.7150/thno.43894.

NLM
Chen W, Zai W, Fan J, Zhang X, Zeng X, Luan J, Wang Y, Shen Y, Wang Z, Dai S, Fang S, Zhao Z, Ju D. Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury. Theranostics 2020; 10(13):5879-5894. doi:10.7150/thno.43894. https://www.thno.org/v10p5879.htm

CSE
Chen W, Zai W, Fan J, Zhang X, Zeng X, Luan J, Wang Y, Shen Y, Wang Z, Dai S, Fang S, Zhao Z, Ju D. 2020. Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury. Theranostics. 10(13):5879-5894.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use