Disease relevance of Fbln5

• Pelvic organ prolapse in Fbln5(-/-) mice was remarkably similar to that in primates [1].
• This phenotype, which resembles the cutis laxa syndrome in humans, reveals a critical function for fibulin-5 as a scaffold protein that organizes and links elastic fibres to cells [2].
• To further examine the role of fibulin-5 during repair of lung injury, we assessed fibulin-5 expression during elastase-induced emphysema in C57/b mice [3].
• A T-cell lymphoblastic lymphoma/leukemia (A55) and a B-cell lymphoblastic lymphoma/leukemia (A31) produced enhanced infiltration of the lung when 10 Gy of total body irradiation (TBI) was given 90 days before the tumor cells [4].

High impact information on Fbln5

• These data suggest that fibulin-5 could be a novel therapeutic target for elastic fiber regeneration [5].
• Deposition of fibulin-5 on microfibrils promotes coacervation and alignment of tropoelastins on microfibrils, and also facilitates cross-linking of tropoelastin by tethering lysyl oxidase-like 1, 2, and 4 enzymes [5].
• Altered vascular remodeling in fibulin-5-deficient mice reveals a role of fibulin-5 in smooth muscle cell proliferation and migration [6].
• Therefore, to clarify the potential role of elastic fiber assembly in the pathogenesis of pelvic organ prolapse, pelvic organ support was characterized in Fbln5(-/-) mice, and changes in elastic fiber homeostasis in the mouse vagina during pregnancy and parturition were determined [1].
• Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor-beta and affects protein kinase cascades [7].

Biological context of Fbln5

• Together with the phenotype of Fbln5(-/-) mice, the results suggest that synthesis and assembly of elastic fibers are crucial for recovery of pelvic organ support after vaginal delivery and that disordered elastic fiber homeostasis is a primary event in the pathogenesis of pelvic organ prolapse in mice [1].
• These results suggest that fibulin-5 and elastic fibers are not directly involved in short-term wound healing [8].
• Normal wound healing in mice deficient for fibulin-5, an elastin binding protein essential for dermal elastic fiber assembly [8].

Anatomical context of Fbln5

• We report that fibulin-5 protein potently induces elastic fiber assembly and maturation by organizing tropoelastin and cross-linking enzymes onto microfibrils [5].
• The closely parallel alterations in elastogenesis associated with increased fibulin-2 in hypodermal connective tissues and decreased fibulin-5 at the hypodermal M-CT interface suggest that these proteins mediate the effect of Tsk-fibrillin-1 on elastogenesis [9].
• Fibulin-5 protein was localized to the fibroblast cell layer in culture, and brief elastase treatment degraded the protein [3].
• Fibulin-5 was localized to pulmonary arteries and associated with thickened elastic laminae [10].
• Importantly, the decrease in tissue-bound ecSOD levels in aortas from fibulin-5-/- mice was associated with an increase in vascular O2*- levels [11].

Associations of Fbln5 with chemical compounds

• Fibulin-5 is also induced in adult lung following lung injury by hyperoxia [3].
• The hydrophobic core of the protein is made up of residues L5, V6, L51, A55, and by the eight cysteine residues [12].

Regulatory relationships of Fbln5

• Our results indicate that fibulin-5 is coordinately expressed and regulated with elastin in lung fibroblasts and may serve a key role during lung injury and repair [3].

Other interactions of Fbln5

• Fibulin-2 and fibulin-5 alterations in tsk mice associated with disorganized hypodermal elastic fibers and skin tethering [9].

Analytical, diagnostic and therapeutic context of Fbln5

• Notably, recombinant fibulin-5 protein induced elastogenesis even in serum-free conditions, although elastogenesis in cell culture has been believed to be serum-dependent [5].
• Immunohistochemistry studies showed that fibulin-5 was induced in cells within the alveolar wall following elastase treatment [3].

References