title: Redefining the roles of p38 and JNK signaling in cardiac hypertrophy: dichotomy between cultured myocytes and animal models.
abstract: The mitogen-activated protein kinase (MAPK) signaling pathways serve as pivotal transducers of diverse biologic functions including cell growth, differentiation, proliferation, and apoptosis. The c-Jun N-terminal kinases (JNKs) and p38 kinases constitute two important branches of the greater MAPK signaling cascade that function as specialized transducers of stress or injury responses, hence they are subclassified as stress-activated protein kinases (SAPKs). In the myocardium, both p38 and JNK transduction cascades have been implicated in regulating the hypertrophic response, as well as cardiomyopathy and heart failure. Most reports proposing a pro-hypertrophic regulatory role for JNK and p38 signaling placed a heavy or exclusive reliance on culture-based models of cellular growth. More recently, a number of studies in genetically modified animal models have challenged the previously proposed role of JNK and p38 as pro-hypertrophic signaling effectors in the myocardium. This review will discuss an increasing body of evidence suggesting that the SAPKs (JNK and p38) do not positively regulate cardiac hypertrophy in vivo, but in fact may actually serve as negative regulators of this response in the adult heart. However, SAPK signaling is likely maladaptive, despite its putative anti-hypertrophic role in vivo, given the observation of dilated cardiomyopathy and heart failure in gain-of-function transgenic models.
authors.affiliation: Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
authors.forename: Qiangrong
authors.initials: Q
authors.lastname: Liang
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Molkentin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019703:Calcineurin; D006332:Cardiomegaly / Q000201:enzymology; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D032342:Muscle Cells / Q000166:cytology* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D019703:Calcineurin