Purinergic signalling in liver diseases: Pathological functions and therapeutic opportunitiesKey points
Ping Wang,
Jidong Jia,
Dong Zhang
Affiliations
Ping Wang
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis & National Clinical Research Center for Digestive Diseases, Beijing 100050, China
Jidong Jia
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis & National Clinical Research Center for Digestive Diseases, Beijing 100050, China; Liver Research Center, Beijing Friendship Hospital, Yong An Road No.95, Xi Cheng District, Beijing 100050, China. Tel.: 86-13501378269; fax: 86-10-63139246.
Dong Zhang
Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation & National Clinical Research Center for Digestive Diseases, Beijing 100050, China; Corresponding authors. Addresses: Experimental and Translational Research Center, Beijing Friendship Hospital, Yong An Road No.95, Xi Cheng District, Beijing 100050, China. Tel.: 86-13911067396; fax: 86-10-63139246.
Summary: Extracellular nucleotides, including ATP, are essential regulators of liver function and serve as danger signals that trigger inflammation upon injury. Ectonucleotidases, which are expressed by liver-resident cells and recruited immune cells sequentially hydrolyse nucleotides to adenosine. The nucleotide/nucleoside balance orchestrates liver homeostasis, tissue repair, and functional restoration by regulating the crosstalk between liver-resident cells and recruited immune cells. In this review, we discuss our current knowledge on the role of purinergic signals in liver homeostasis, restriction of inflammation, stimulation of liver regeneration, modulation of fibrogenesis, and regulation of carcinogenesis. Moreover, we discuss potential targeted therapeutic strategies for liver diseases based on purinergic signals involving blockade of nucleotide receptors, enhancement of ectonucleoside triphosphate diphosphohydrolase activity, and activation of adenosine receptors.
