Apelin Liver Signaling Pathway

The apelin gene is X-linked and is synthesized as a 77 amino acid pre-pro-peptide that is cleaved post-translationally to generate several active forms whose lengths range from 36 to 12 amino acids. These isoforms possess similar functions but display different tissue distribution, potency and receptor binding affinity. Apelin acts as a ligand for the APJ receptor (angiotensin II receptor like-1, AT-1), which is coupled to pertussis toxin (PTX)-sensitive G proteins. The apelin/APJ system plays important and various roles in the physiology and pathophysiology of many organs, including regulation of blood pressure, angiogenesis, cardiac contractility, metabolic balance, cell proliferation and apoptosis. It is noteworthy that the APJ receptor is also activated by APELA, a distinct peptide hormone with significant effects on cardiac development.Apelin has negative effects on hepatic recovery from injury- promoting inflammation, apoptosis, angiogenesis, fibrosis, and inhibiting regeneration. Its mode of action is at least in part through JNK and FAS, as well as increased expression of the PDGF receptor. It is induced during liver injury, at least in part by the preceding production of angiotensin II and endothelin, and is one of the major mediators of their damaging effects.