Disease relevance of Fbln1

• Attempts to rescue the placental phenotypes of a congenic model of interspecies hybrid placental dysplasia (IHPD) by normalizing expression of Fbln1 proved that Fbln1 alone is not the key cause of phenotypes in these models of placental hyperplasia [1].
• MEM-2 represents a useful new tool for the study of Fbln-1 in breast cancer [2].

High impact information on Fbln1

• Endostatins and NC1 showed a comparable binding activity for the microfibrillar fibulin-1 and fibulin-2, and for heparin [3].
• No significant immunological cross-reaction could be detected between fibulin-1 and fibulin-2 [4].
• Fibulin (fbln)-5 is an elastin-binding protein required for assembly and organization of elastic fibers [5].
• Immunohistology demonstrated the absence of fibulin-1 in its typical localizations but no aberrant patterns for several other extracellular matrix proteins [6].
• Perinatal lethality and endothelial cell abnormalities in several vessel compartments of fibulin-1-deficient mice [6].

Biological context of Fbln1

• Fibulin-1 is particularly well expressed in the endocardial cushion tissue (ECT) during embryogenesis and we therefore compared the expression patterns of fibulin-1 and -2 in the developing mouse heart [7].
• By searching the database we identified most of the exons encoding the human fibulin-1 gene and showed that its exon-intron organization is similar to that of the mouse gene [8].
• Fibulin-1 and fibulin-2 expression during organogenesis in the developing mouse embryo [9].
• Here, we show that a murine placental overgrowth phenotype is associated with elevated Fbln1 transcript levels, suggesting that the gene and its product have a functional role in placentation [1].
• Absence of fibulin-1 caused considerable blood loss but did not compromise blood clotting [6].

Anatomical context of Fbln1

• Sequence of extracellular mouse protein BM-90/fibulin and its calcium-dependent binding to other basement-membrane ligands [10].
• Fibulin-2 was found to be a more specific marker for the embryonic ECT than fibulin-1, which was also transiently expressed in cardiac muscle [7].
• Fibulin-1 mRNA was also expressed in the epidermal layer of brain and in the mesenchyme of choroid plexus and the meninges which surround the spinal cord [9].
• These studies show that the differential expression of the fibulin family contributes to the formation of molecularly distinct extracellular matrices already during early developmental stages of a large number of tissues [9].
• In addition, a locally restricted expression pattern of fibulin-1 and fibulin-2 mRNA and protein at sites of epithelial-mesenchymal interactions was detected in two tissues, the developing tooth and hair follicles [9].

Associations of Fbln1 with chemical compounds

• Self aggregation into nest-like oligomers was observed at high concentrations of fibulin-1 which was not sensitive to EDTA [11].
• Evidence that fibulin family members contribute to the steroid-dependent extravascular sequestration of sex hormone-binding globulin [12].
• Fibulin-1 is a calcium-binding glycoprotein present in the extracellular matrix and in the serum [13].
• Cultured human endometrial stromal cells treated with progesterone responded with a dramatic increase of fibulin-1 protein expression [14].
• Altogether the results show a cycle-dependent regulation of endometrial fibulin-1 expression controlled by both progesterone and estrogen [14].
• We found that the recombinant TM14 protein was glycosylated with N-linked oligosaccharides and interacted with heparin, fibronectin, fibulin-1, and dentin sialophosphoprotein [15].

Regulatory relationships of Fbln1

• Our studies show that fibulin-1 is expressed surrounding the primordial VSMCs of the vessel wall before elastin precursors are present and suggest that differential expression of the JB3 antigen (Wunsch et al., 1994) may be indicative of early diversity among embryonic VSMCs [16].

Other interactions of Fbln1

• Different susceptibilities of fibulin-1 and fibulin-2 to cleavage by matrix metalloproteinases and other tissue proteases [17].
• Fibulin-1 (95 kDa) was readily cleaved by leucocyte elastase, weakly by matrilysin and not by the other proteases [17].
• The laminin connector molecule, nidogen-1, had a distribution similar to that of laminin beta(1) and gamma(1), whereas fibulin-1 and -2, which compete with nidogen-1, were mostly confined to blood vessels [18].
• The extracellular matrix protein fibulin-1 (FBLN1) is an important component of blood vessel walls, as shown by the lethality of mice with homozygous targeted deletion of the Fbln1 gene [1].
• The protein BM-90 was solubilized from the mouse Engelbreth-Holm-Swarm tumor with neutral buffers in molar yields lower (15-30%) than found for other basement membrane proteins (e.g. laminin, BM-40) [19].

Analytical, diagnostic and therapeutic context of Fbln1

• In this study, a complete sequence analysis of mouse BM-90 cDNA showed a 539-residue N-terminal core structure (domains I and II), which was 85% identical with the same core structure of human fibulin [10].
• Antibodies against mouse fibulin-1 and -2 were used in immunofluorescence, and the expression of mRNAs were studied with synthetic oligonucleotides by in situ hybridization [7].
• We used in situ hybridization and immunofluorescence staining to examine the expression of fibulin-1 and fibulin-2 during mouse embryogenesis [9].
• This review summarizes findings from studies of animal models of fibulin deficiency, human fibulin gene mutations, human tumours and injury models that have advanced our understanding of the normal and pathological roles of members of this formerly obscure family [20].
• Primers were derived for RT-PCR analysis of fibulin-1 expression in rat endometrium [14].

References