TY - JOUR
T1 - Pathological roles of purinergic signaling in the liver
AU - Vaughn, Byron P.
AU - Robson, Simon C.
AU - Burnstock, Geoffrey
PY - 2012/10
Y1 - 2012/10
N2 - Purinergic signaling has been postulated as a mechanism of cellular signaling since the early 1970s. Cellular responses triggered by extracellular nucleotides and nucleosides occur by defined adenosine (P1) and ATP (P2) receptors, respectively, and play a prominent role in many aspects of health and disease, including those involving the liver. In normal physiology, extracellular nucleotides modulate many of the normal biologic and hepatic metabolic processes such as gluconeogenesis and insulin responsiveness. Further, in multiple disease states, ATP and certain nucleotides serve as danger signals and are involved in heightened purinergic receptor activation in a myriad of pathologic processes. Recently, others and we have shown the regulation of purinergic signaling by ectonucleotidases to play an important role in the acute vascular pathobiology of liver inflammation, regeneration, and immunity, as in ischemia reperfusion and transplantation. Increased understanding into mechanisms of extracellular ATP metabolism by such ecto enzymes has also led to novel insights into the exquisite balance of nucleotide P2-receptor and adenosinergic P1-receptor signaling in those chronic hepatic diseases characterized by steatosis, fibrosis, and malignancy. This review will explore the developing role of purinergic signaling in the pathophysiology of liver disease and comment on potential future clinical applications.
AB - Purinergic signaling has been postulated as a mechanism of cellular signaling since the early 1970s. Cellular responses triggered by extracellular nucleotides and nucleosides occur by defined adenosine (P1) and ATP (P2) receptors, respectively, and play a prominent role in many aspects of health and disease, including those involving the liver. In normal physiology, extracellular nucleotides modulate many of the normal biologic and hepatic metabolic processes such as gluconeogenesis and insulin responsiveness. Further, in multiple disease states, ATP and certain nucleotides serve as danger signals and are involved in heightened purinergic receptor activation in a myriad of pathologic processes. Recently, others and we have shown the regulation of purinergic signaling by ectonucleotidases to play an important role in the acute vascular pathobiology of liver inflammation, regeneration, and immunity, as in ischemia reperfusion and transplantation. Increased understanding into mechanisms of extracellular ATP metabolism by such ecto enzymes has also led to novel insights into the exquisite balance of nucleotide P2-receptor and adenosinergic P1-receptor signaling in those chronic hepatic diseases characterized by steatosis, fibrosis, and malignancy. This review will explore the developing role of purinergic signaling in the pathophysiology of liver disease and comment on potential future clinical applications.
KW - CD39
KW - CD73
KW - Ectonucleotidases
KW - Liver disease
KW - P2-receptor
KW - T lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=84866409390&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866409390&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2012.06.008
DO - 10.1016/j.jhep.2012.06.008
M3 - Comment/debate
C2 - 22709619
AN - SCOPUS:84866409390
SN - 0168-8278
VL - 57
SP - 916
EP - 920
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -