Prokineticin receptors in cardiovascular function: foe or friend?
Prokineticins are small secreted bioactive peptides, comprising two classes: prokineticin-1 and prokineticin-2. They exert their biological activity by binding to two G-protein-coupled receptors: prokineticin receptor (PKR) 1 and 2. Recent data have demonstrated that PKR1 induces postnatal neovasculogenesis by activating adult epicardial-derived progenitor cell differentiation, whereas myocardial PRK2 signaling confers detrimental actions on cardiomyocytes, leading to dilated cardiomyopathy and release of an unknown paracrine factor to induce capillary fenestration and vascular leakage. The knowledge gained from these studies leads to a model in which PKR1 and PKR2 signaling exert opposing actions in heart physiology and pathophysiology and facilitate the discovery of specific agonists and antagonists targeting PKR1 and PKR2 for possible use in treatment of cardiovascular diseases.
Nebigil
Canan G
CG
CNRS, Université de Strasbourg, FRE 3211 Ecole Supérieure de Biotechnologie de Strasbourg, F-67412 Illkirch, France. canan.nebigil@unistra.fr
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000378:metabolism; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000378:metabolism; D015316:Genetic Therapy; D006331:Heart Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D009203:Myocardial Infarction / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D009479:Neuropeptides / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000378:metabolism
D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C525015:PKR1 protein, mouse; C525016:PKR2 protein, mouse; C423608:PROK2 protein, human; C470837:PROKR1 protein, human; C470838:PROKR2 protein, human; C486586:Prok2 protein, mouse; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived