Theranostics 2021; 11(7):3317-3330. doi:10.7150/thno.55795


Organ-organ communication: The liver's perspective

Fei Wang1, Kwok-Fai So2,3, Jia Xiao4✉, Hua Wang5,6✉

1. Division of Gastroenterology, Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
2. GMH Institute of CNS Regeneration, Guangdong Medical Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, China.
3. Laboratory of Neuroendocrinology, Fujian Key Laboratory of Developmental and Neurobiology, School of Life Sciences, Fujian Normal University, Fuzhou, China.
4. Clinical Medicine Research Institute and Department of Interventional Surgery, First Affiliated Hospital of Jinan University, Guangzhou, China.
5. Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China.
6. Inflammation and Immune Mediated Disease Laboratory of Anhui Province; School of Pharmacy, Anhui Medical University, Hefei, China.

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Wang F, So KF, Xiao J, Wang H. Organ-organ communication: The liver's perspective. Theranostics 2021; 11(7):3317-3330. doi:10.7150/thno.55795. Available from

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Communication between organs participates in most physiological and pathological events. Owing to the importance of precise coordination among the liver and virtually all organs in the body for the maintenance of homeostasis, many hepatic disorders originate from impaired organ-organ communication, resulting in concomitant pathological phenotypes of distant organs. Hepatokines are proteins that are predominantly secreted from the liver, and many hepatokines and several signaling proteins have been linked to diseases of other organs, such as the heart, muscle, bone, and eyes. Although liver-centered interorgan communication has been proposed in both basic and clinical studies, to date, the regulatory mechanisms of hepatokine production, secretion, and reciprocation with signaling factors from other organs are obscure. Whether other hormones and cytokines are involved in such communication also warrants investigation. Herein, we summarize the current knowledge of organ-organ communication phenotypes in a variety of diseases and the possible involvement of hepatokines and/or other important signaling factors. This provides novel insight into the underlying roles and mechanisms of liver-originated signal transduction and, more importantly, the understanding of disease in an integrative view.

Keywords: Liver, Organ communication, Hepatokine, Cytokine, Disease mechanism.