The Role of Oncostatin M and Its Receptor Complexes in Cardiomyocyte Protection, Regeneration, and Failure.
Thomas KubinPraveen GajawadaPeter BramlageStefan HeinBenedikt BergeAyse CetinkayaHeiko BurgerMarkus SchönburgWolfgang SchaperYeong-Hoon ChoiManfred RichterPublished in: International journal of molecular sciences (2022)
Oncostatin M (OSM), a member of the interleukin-6 family, functions as a major mediator of cardiomyocyte remodeling under pathological conditions. Its involvement in a variety of human cardiac diseases such as aortic stenosis, myocardial infarction, myocarditis, cardiac sarcoidosis, and various cardiomyopathies make the OSM receptor (OSMR) signaling cascades a promising therapeutic target. However, the development of pharmacological treatment strategies is highly challenging for many reasons. In mouse models of heart disease, OSM elicits opposing effects via activation of the type II receptor complex (OSMR/gp130). Short-term activation of OSMR/gp130 protects the heart after acute injury, whereas chronic activation promotes the development of heart failure. Furthermore, OSM has the ability to integrate signals from unrelated receptors that enhance fetal remodeling (dedifferentiation) of adult cardiomyocytes. Because OSM strongly stimulates the production and secretion of extracellular proteins, it is likely to exert systemic effects, which in turn, could influence cardiac remodeling. Compared with the mouse, the complexity of OSM signaling is even greater in humans because this cytokine also activates the type I leukemia inhibitory factor receptor complex (LIFR/gp130). In this article, we provide an overview of OSM-induced cardiomyocyte remodeling and discuss the consequences of OSMR/gp130 and LIFR/gp130 activation under acute and chronic conditions.
Keyphrases
- left ventricular
- heart failure
- aortic stenosis
- high glucose
- endothelial cells
- drug induced
- angiotensin ii
- stem cells
- aortic valve
- transcatheter aortic valve replacement
- acute myeloid leukemia
- ejection fraction
- aortic valve replacement
- bone marrow
- atrial fibrillation
- liver failure
- transcatheter aortic valve implantation
- coronary artery disease
- pulmonary hypertension
- respiratory failure
- cardiac resynchronization therapy
- living cells
- sensitive detection
- pluripotent stem cells
- acute heart failure