transforming-growth-factor-beta and Acromegaly

Although historically Marfan syndrome (MFS) has always been considered as a condition caused by the deficiency of a structural extracellular matrix protein, fibrillin-1, the study of Marfan mouse models and Marfan-related conditions has shifted our current understanding to a pathogenic model that involves dysregulation of the cytokine-transforming growth factor beta (TGF-β) signaling.. In this review, we focus on the impact of the revised MFS clinical diagnostic criteria. We discuss lessons that have been learned from molecular findings in relevant Marfan-related conditions, such as sporadic thoracic aortic aneurysm/dissection, stiff skin syndrome, acromelic dysplasias and Loeys-Dietz syndrome. We explore the latest insights into the role of the alternative TGF-β signaling pathways in MFS pathogenesis. Finally, we give an update on the current and future treatment strategies.. The recent insights into the pathogenesis of MFS and related disorders have offered a prime example of translational medicine with immediate bridge between molecular findings and therapeutic options.

Topics: Acromegaly; Adolescent; Aortic Aneurysm, Thoracic; Child; Child, Preschool; Female; Fibrillin-1; Fibrillins; Humans; Loeys-Dietz Syndrome; Male; Marfan Syndrome; Microfilament Proteins; Mutation; Signal Transduction; Transforming Growth Factor beta

The growth hormone (GH)-insulin-like growth factor (IGF)-I axis is an important modulator of growth and development, but in addition to their classical role as endocrine hormones, its components also regulate a wide range of biological functions through paracrine and autocrine mechanisms. Their potent mitogenic and anti-apoptotic effects play a critical role in the regulation of rapidly renewing epithelial cell populations such as those found in the colon. Recent evidence suggests an association between inappropriate regulation of the GH-IGF-I axis and the development of colorectal cancer. However, the molecular mechanisms and signalling pathways responsible are only beginning to be unravelled, as are the relative contributions of the endocrine and autocrine or paracrine effects.

Topics: Acromegaly; Animals; Apoptosis; Colorectal Neoplasms; Cyclooxygenase 2; Endothelial Growth Factors; Growth Hormone; Humans; Immune Tolerance; Insulin-Like Growth Factor Binding Proteins; Isoenzymes; Lymphokines; Membrane Proteins; Neovascularization, Pathologic; Prostaglandin-Endoperoxide Synthases; Receptors, Somatomedin; Signal Transduction; Somatomedins; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Topics: Acromegaly; Animals; Cardiomegaly; Chalones; Humans; Insulin-Like Growth Factor I; Mitogen-Activated Protein Kinase Kinases; Myocardial Infarction; Myocardium; Myostatin; Organ Size; Signal Transduction; Transforming Growth Factor beta