Disease relevance of Fbn1

• Induction and coexpression of latent transforming growth factor beta-binding protein-1 and fibrillin-1 in experimental glomerulonephritis [1].
• We conclude that fibrillin-1 may contribute to glomerular damage in hypertensive and diabetic kidney disease [2].
• Defects in fibrillin-1 predisposes individuals to vascular damage in Marfan syndrome, but the role of fibrillin-1 in kidney disease is unknown [2].
• To test the functional role of fibrillin-1, DOCA hypertension and STZ diabetes were induced in mice homozygous for a mutation leading to a fivefold lower expression of fibrillin-1 (mgR/mgR) [2].
• On the other hand, albuminuria as a parameter of microvascular damage in hypertension and diabetes was ameliorated in fibrillin-1-underexpressing mice, possibly due to a compensatory upregulation of decorin [2].

High impact information on Fbn1

• DOCA-salt hypertension or streptozotocin (STZ) diabetes led to a significant increase in glomerular fibrillin-1 deposition [2].
• RESULTS: Induction of glomerular LTBP-1 mRNA was detected on day 2 of disease, while mRNA for fibrillin-1 was already upregulated 1 day after induction of disease [1].
• Biochemical quantitation and Western blot analysis of main extracellular matrix proteins on GD 20 showed no overt difference in expression of collagen type I, fibrillin-1, or elastin [3].
• In situ hybridization and immunofluorescence studies indicated that at day 15 of gestation, fibrillin-1 is expressed in the metanephric mesenchyme [4].
• Fibrillin-1 cDNA was isolated from the rat kidney cDNA library and sequenced, and its spatiotemporal expression was studied [4].

Biological context of Fbn1

• These data indicate that, like alphavbeta3 integrin, a known morphogen and a putative receptor of fibrillin-1, the fibrillin-1 modulates events related to early organogenesis and possibly also the vascularization of the rat kidney [4].
• It had approximately 88% homology with human fibrillin-1 and had Ca2+ binding epidermal growth factor-like domains, transforming growth factor-beta binding protein motifs, and an RGD binding site [4].
• The expression of types X and VI collagen and fibrillin in rat mandibular condylar cartilage. Response to mastication forces [5].

Anatomical context of Fbn1

• Type VI collagen and fibrillin were synthesized by cells in the perichondrium-periosteum and by chondrocytes and by stromal osteoblasts and were not modified by higher mechanical forces [5].
• Types X and VI collagen and fibrillin were localized by in situ hybridization and immunohistochemical methods in the mandibular condyles of rats, and the response of these molecules to post-weaning diets of soft food, ordinary pellets, or hardened pellets was studied [5].

Analytical, diagnostic and therapeutic context of Fbn1

• Real-time RT-PCR and immunohistochemical analyses for LTBP-1 and fibrillin-1 were performed [1].
• Thus underexpression of fibrillin-1 predisposes individuals to lethal aortic dissection in the presence of hypertension [2].
• Northern blot analysis revealed an approximately 10-kb transcript, and fibrillin-1 expression was developmentally regulated [4].

References