Pathophysiology of hepatic Na+/H+ exchange (Review).

Na+/H+ exchangers (NHEs) are a family of membrane proteins that contribute to exchanging one intracellular proton for one extracellular sodium. The family of NHEs consists of nine known members, NHE1-9. Each isoform represents a different gene product that has unique tissue expression, membrane localization, physiological effects, pathological regulation and sensitivity to drug inhibitors. NHE1 was the first to be discovered and is often referred to as the 'housekeeping' isoform of the NHE family. NHEs are not only involved in a variety of physiological processes, including the control of transepithelial Na+ absorption, intracellular pH, cell volume, cell proliferation, migration and apoptosis, but also modulate complex pathological events. Currently, the vast majority of review articles have focused on the role of members of the NHE family in inflammatory bowel disease, intestinal infectious diarrhea and digestive system tumorigenesis, but only a few reviews have discussed the role of NHEs in liver disease. Therefore, the present review described the basic biology of NHEs and highlighted their physiological and pathological effects in the liver.