The Tight skin (Tsk) mutation is a duplication of the mouse fibrillin 1 (Fbn1) gene that results in a larger (418 kD) than normal (350 kD) protein; Tsk/+ mice display increased connective tissue, bone overgrowth, and lung emphysema. Lung emphysema, bone overgrowth, and vascular complications are the distinctive traits of mice with reduced Fbn1 gene expression and of Marfan syndrome (MFS) patien...

RATIONALE Mutations in fibrillin-1 are associated with thoracic aortic aneurysm (TAA) in Marfan syndrome. Genome-wide association studies also implicate fibrillin-1 in sporadic TAA. Fragmentation of the aortic elastic lamellae is characteristic of TAA. OBJECTIVE Immunoassays were generated to test whether circulating fragments of fibrillin-1, or other microfibril fragments, are associated wit...

Changes in the structure and metabolism of fibrillin, a microfibril associated protein, can result in classical Marfan syndrome, and reduced expression of decorin, a small extracellular chondroitin sulphate/dermatan sulphate proteoglycan, has been observed in fibroblasts of a patient with neonatally lethal Marfan syndrome. We have studied the synthesis of fibrillin and decorin in cultured fibro...

Fibrillin-1 localization in the myocardium and the modulation of its expression in cardiac fibrosis were examined. In normal rat hearts, fibrillin-1 was abundant throughout the myocardium as thin fibers that crossed over the perimysium and around arteries. After cardiac fibrosis was induced in rats by either 14-day ANG II infusion or 21-day DOCA-salt treatment [a high endothelin-1 (ET-1) model]...

PURPOSE Pelvic organ prolapse is a multifactorial disorder in which extracellular matrix defects are implicated. Fibrillin-1 level is reduced in stress urinary incontinence. In Marfan syndrome, which is associated with mutations in Fibrillin-1, pelvic floor disorders are commonly observed. We hypothesize that Fibrillin-1 gene expression is altered in pelvic organ prolapse. METHODS Thirty wome...

Fibrillins are large cysteine-rich glycoproteins (~350 kDa) which form the molecular scaffold of a class of beaded microfibrils that are key structural elements of dynamic connective tissues (Kielty and Shuttleworth, 1995). These microfibrils are extensible polymers which act as a structural lattice for elastin deposition during elastic fibre formation (Mecham and Heusar, 1991). Linkage of the ...

The microfibrillar protein fibrillin-1 is a component of the mesangial matrix. Defects in fibrillin-1 predisposes individuals to vascular damage in Marfan syndrome, but the role of fibrillin-1 in kidney disease is unknown. We hypothesized that fibrillin-1 is involved in hypertensive or diabetic glomerular disease. DOCA-salt hypertension or streptozotocin (STZ) diabetes led to a significant incr...

Microfibrils are essential elements in elastic and nonelastic tissues contributing to homeostasis and growth factor regulation. Fibrillins form the core of these multicomponent assemblies. Various human genetic disorders, the fibrillinopathies, arise from mutations in fibrillins and are frequently associated with aberrant microfibril assembly. These disorders include Marfan syndrome, Weill-Marc...

INTRODUCTION: It has been suggested that the elastic network plays an important role in the tissue response to mechanical stress. The components of the elastic network have been poorly studied in liver diseases. Therefore, in this work, the expression and distribution of fibrillin-1 and elastin were studied in hepatic focal nodular hyperplasia and compared with surrounding liver and hepatocellu...

Secreted metalloproteases have diverse roles in the formation, remodeling, and the destruction of extracellular matrix. Recessive mutations in the secreted metalloprotease ADAMTS17 cause ectopia lentis and short stature in humans with Weill-Marchesani-like syndrome and primary open angle glaucoma and ectopia lentis in dogs. Little is known about this protease or its connection to fibrillin micr...