title: Decreased extracellular deposition of fibrillin and decorin in neonatal Marfan syndrome fibroblasts.
abstract: Abnormalities of the microfibrillar protein fibrillin (Fib) have been reported in Marfan syndrome (MFS). The so-called neonatal Marfan syndrome (nMFS) is a lethal phenotype displaying features that are not seen in classical MFS. We have therefore studied the biosynthesis and extracellular deposition of Fib and decorin in fibroblasts from a patient with nMFS and controls. Immunofluorescence of the patient's cell cultures showed an almost complete absence of Fib and a marked reduction of decorin in the extracellular matrix (ECM). The nMFS skin revealed Fib on subbasal microfibrillar bundles in the papillary dermis, and Fib associated with elastic fibers in the reticular dermis; the bundles and fibers were fragmented and thinner than normal. Pulse-chase labeling of cells with [35S]Met/Cys revealed moderately reduced secretion, but a diminished deposition of Fib in the ECM; this was more apparent at a longer chase time. Fib mRNA and synthesis appeared to be normal, whereas both decorin mRNA and biosynthesis were reduced. We therefore assume a structural Fib defect in this patient causing reduced deposition into and/or enhanced removal from the ECM, whereas the reduced decorin biosynthesis may be a secondary regulatory phenomenon. The clinical relevance of this remains unclear. Our findings imply that Fib defects may be responsible for the severe, complex phenotype of nMFS.
authors.affiliation: Stoffwechselabteilung der Universitätskinderklinik, Zürich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Raghunath
authors.forename: A
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: M
authors.initials: M
authors.lastname: Godfrey
authors.forename: B
authors.initials: B
authors.lastname: Steinmann
mesh_terms: D015152:Blotting, Northern; D058575:Decorin; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D000071837:Fibrillins; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D011509:Proteoglycans / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D000071837:Fibrillins; D008840:Microfilament Proteins; D011509:Proteoglycans