title: [Interactions between fibrillin-1 and tgf-beta: consequences and human pathology].
abstract: Fibrillin-1 (FBN-1) is the main component of the 10-12 nm microfibrils found in the extracellular matrix (ECM). ECM displays a structural role in the tissue-specific organization and takes part in the regulation of various cytokines and growth factors. A growing body of evidences supports a narrow relationship between FBN-1 and TGF-beta. Homology between FBN-1 and latent TGF-beta (LTGF) allows microfibrills to be a reservoir for this cytokine. The Marfan syndrome (MFS), a prototypic fibrillinopathy, highlights these relationships as it relates to 2 major genes that are FBN1 and TGF-beta type II receptor (TGFBR2) genes. In a mouse model of MFS, an up-regulation of the TGF-beta pathway is partly responsible for the phenotype. This FBN-1/TGF-beta relationship may play also a role in systemic sclerosis (SSc), a multigenic disease characterized by excessive generalised ECM deposit. Indeed, two related animal models results from both gene mutations: the Tight Skin 1 mouse is due to a partial in-frame duplication of the Fbn1 gene and another model conditionally overexpresses TGF-beta type I receptor. A better understanding of FBN-1/TGF-beta relationship appears of great importance in fibrillinopathies: it may allow reconsidering the nosologic framework of these diseases including the TGF-beta signalopathies and could lead to innovative therapeutic strategies.
authors.affiliation: Inserm U781, Université Paris Descartes, Hôpital Necker, 149, rue de Sèvres, 75015 Paris, France. julien.wipff@cch.aphp.fr
authors.forename: Julien
authors.initials: J
authors.lastname: Wipff
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
mesh_terms: D005109:Extracellular Matrix / Q000502:physiology; D000071838:Fibrillin-1; D000071837:Fibrillins; D006706:Homeostasis; D006801:Humans; D008382:Marfan Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008840:Microfilament Proteins / Q000235:genetics* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D012595:Scleroderma, Systemic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000502:physiology*; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse