| Transforming Growth Factor β Signaling Perturbation in the Loeys-Dietz Syndrome. | |
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MedLine Citation:
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PMID: 22335518 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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The transforming growth factor β (TGFβ) superfamily consists of multipotential secreting cytokines that mediate many key events in normal cellular growth and development, including differentiation, proliferation, motility, organization and death. TGFβs act as ligand for 3 classes of cell surface receptors, the transmembrane serine-threonine kinase receptors, TGFβ receptor type I (TGFβRI) and type 2 (TGFβRII), and TGFβRIII receptors which include an ubiquitous extracellular β-glycan and the membrane glycoprotein endoglin (CD105). Binding of TGFβs to their receptors initiates diverse cellular responses resulting in the phosphorilation of Smad proteins, which then translocate to the nucleus and regulate the transcription of target genes. Perturbation of TGFβ signaling has been implicated in various human disorders including cancer, fibrosis and auto-immune diseases. Recently, mutations in TGFβR1 and TGFβR2 genes have been found in association with a continuum of clinical features with widespread vascular involvement. The extreme of clinical severity is represented by the Loeys-Dietz syndrome (LDS), an autosomal dominant disorder characterized by hypertelorism, bifid uvula, and/or cleft palate, and aggressive arteriopathy causing arterial tortuosity as well as life-threatening complications such as vascular aneurysms and dissections. Elastin disarray, loss of elastic fibre architecture and increased collagen expression in the arterial wall are the pathologic hallmark of LDS. In the present review article we will provide details on the activation of TGFβ cascade, on the clinical features of LDS, as well as on the mechanisms of TGFβ signaling perturbation leading to this condition and the potential role of the antagonism of TGFβ activity in disease management. |
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Authors:
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A Pezzini; E Del Zotto; A Giossi; I Volonghi; P Costa; A Padovani |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Current medicinal chemistry Volume: 19 ISSN: 1875-533X ISO Abbreviation: Curr. Med. Chem. Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-02-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9440157 Medline TA: Curr Med Chem Country: Netherlands |
Other Details:
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Languages: eng Pagination: 454-60 Citation Subset: IM |
Affiliation:
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Dipartimento di Scienze Mediche e Chirurgiche, Clinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili, 1, 25100 Brescia, Italia. ale_pezzini@hotmail.com. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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