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EMBO reports 4, 12, 1127–1131 (2003)
doi:10.1038/sj.embor.7400033
Fibulins: physiological and disease perspectives
W. Scott Argraves1, Lisa M. Greene2, Marion A. Cooley1 & William M. Gallagher2
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1 Medical University of South Carolina, Department
of Cell Biology, 173 Ashley Avenue,
Charleston, South Carolina 29425,
USA
2 Department of Pharmacology, Conway Institute of
Biomolecular and Biomedical Research, University College Dublin,
Belfield, Dublin 4, Ireland
To whom correspondence should be addressed
W. Scott Argraves Tel: +1 843 792 5482; Fax: +1 843 792 0664;
argraves@musc.edu
William M. Gallagher Tel: +353 1 7166743; Fax: +353 1 2692749;
william.gallagher@ucd.ie
Received 22 August 2003; Accepted 24 October 2003.
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Abstract
The fibulins are a family of proteins that are associated with
basement membranes and elastic extracellular matrix fibres. 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.
EMBO reports 4, 12, 1127–1131 (2003)
doi:10.1038/sj.embor.7400033
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Introduction
In little more than a decade since the discovery of the first fibulin
(Argraves et al., 1989), a six-member family
of extracellular-matrix (ECM) proteins has emerged (Table
1; Fig. 1). The fibulins are minimally defined as
having a series of epidermal growth factor (EGF)-like modules, followed by a
carboxy-terminal fibulin-type module (Fig. 2). It is
evident that the fibulins are an ancient family of proteins, which are highly
conserved in species as evolutionarily distant as worms and humans. Fibulins
have a diverse array of protein ligands (Timpl et
al., 2003; and see
supplementary information online). As a consequence of these widespread
interactions, fibulins are hypothesized to function as intramolecular bridges
that stabilize the organization of supramolecular ECM structures, such as
elastic fibres and basement membranes. Indeed, the family name originates from
the Latin word fibula, which means clasp or buckle. The biophysical
features of the fibulins have been well described in a recent article (Timpl et al., 2003). Here, we place into perspective
findings from many types of studies, including DNA microarray and
gene-targeting experiments, that collectively provide new insights into the
functions of the fibulins under physiological and pathological conditions.
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Table 1
Fibulin family nomenclature
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Figure 1
Modular structures of the fibulins. The most recent addition to the
family, fibulin 6 (hemicentin), was originally identified in the nematode
(Vogel & Hedgecock, 2001), with orthologues in
other species (human, mouse and rat) having now been identified. Nine of the 48
immunoglobulin domains in fibulin 6 are shown (double slashes indicate where
the omitted domains occur). Alternative splice variants are known for fibulins
1–4, albeit only variants for fibulin 1 (designated
A–D) are displayed.
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Figure 2
Alignment of fibulin-type module sequences from the human fibulins.
The carboxy-terminal regions of the fibulins were aligned using ClustalW 1.82,
and Boxshade 3.21 was used to highlight conserved amino acids. Identical
residues are indicated in the blue background and chemically similar residues
with green shading. The GenBank accession numbers for the sequences depicted
are as follows: fibulin 1C, CAA37772.1;
fibulin 1D, AAB17099.1; fibulin 2,
CAA57876.1; fibulin 3,
NP_004096.2; fibulin 4,
CAA10791.2; fibulin 5,
NP_006320.2; fibulin 6,
NP_114141.1.
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Fibulins in elastic fibre biology
There is substantial evidence that implicates the fibulins in both
elastic matrix fibre assembly and function. Fibulins 1, 2 and 5 all bind to
tropoelastin (Nakamura et al., 2002;
Sasaki et al., 1999; Yanagisawa et al., 2002). Early in development,
fibulin 1 is associated with ECM fibres that contain both elastin and the
microfibril-associated proteins fibrillins 1 and 2 (Visconti
et al., 2003). The expression of fibulin 1 during murine lung
development is coordinately expressed with tropoelastin and another
elastin-associated microfibril protein, latent TGF- -binding protein 2
(LTBP2; Mariani et al., 2002). Fibulin 1
also colocalizes with elastin in the core of mature elastin-containing fibres
in skin and blood vessels (Roark et al.,
1995). Unlike fibulin 1, fibulin 2 is found at the interface between
microfibrils and the elastin core (Reinhardt et al.,
1996). The ability of fibulin 2 to bind elastin and fibrillin 1 may
indicate that it anchors fibrillin-containing microfibrils to elastin fibres.
Fibulin 5 binding to both integrins and elastin implicates it as a connector of
elastin fibres to cells (Nakamura et al.,
1999). The interaction of these fibres with the cell surface might be
an integral part of elastic fibre assembly, as for other ECM fibres, such as
fibronectin (FN). In support of this, mice deficient in fibulin 5 have
defective assemblages of elastic fibres (Nakamura et
al., 2002; Yanagisawa et al.,
2002).
Fibulins in cardiovascular biology
Fibulins 1 and 2 are highly expressed during cardiac valvuloseptal
formation. Both are produced by migratory cardiac mesenchymal cells that have
transdifferentiated from endocardial cells (Bouchey et
al., 1996; Tsuda et al.,
2001; Zhang et al., 1995). In
developing and adult heart valves, fibulins 1 and 2 are prominently expressed
and fibulin 4 is moderately expressed (Giltay et al.,
1999; Zhang et al., 1995).
Relatively little fibulin 3 is found in adult heart valves (Giltay et al., 1999). The fact that fibulin 1
deficiency does not result in overt valvuloseptal defects (Kostka et al., 2001) could indicate compensation by
other fibulins.
Fibulins are prominently expressed in blood vessels. During
development, fibulin 1 is expressed by the primordial vascular smooth muscle
cells (VSMCs) that associate with the ventral endothelium of the dorsal aortae
(Hungerford et al., 1997). Primordial VSMCs
of the developing aortic-arch vessels also synthesize fibulin 2. In addition,
fibulin 2 is expressed by coronary endothelial cells (ECs) that originate from
epicardial cells, but it is not expressed by capillary ECs (Tsuda et al., 2001). In adult blood vessels,
pronounced fibulin 1 deposition occurs in the matrix that surrounds VSMCs and
in the elastic laminae of arteries (Roark et al.,
1995). Fibulin 3 expression is prominent in some capillaries, but not
in large blood vessels (Giltay et al.,
1999). Fibulin 3 is highly expressed in human umbilical vein ECs (on
the basis of a GeneAtlas analysis; http://expression.gnf.org), but
its expression is repressed during in vitro human capillary tube
formation (Bell et al., 2001). Fibulin 4 is
found in the medial layers of large veins and arteries and in some small
capillaries (Giltay et al., 1999). Fibulin
5 seems to be restricted to the arterial vasculature and is expressed
predominantly by VSMCs of developing arteries and at low levels by VSMCs of
adult blood vessels (Kowal et al., 1999).
ECs also express fibulin 5, especially the pulmonary artery endothelium
(Jean et al., 2002; Kowal et al., 1999). Fibulin 1 is not generally
expressed in ECs (Roark et al., 1995).
Knockout animal models and heritable diseases in
humans
The importance of the fibulins in development and disease has been
highlighted by gene-targeting experiments in animal models and the
identification of spontaneous mutations in humans. Fibulin 1 deficiency in mice
causes extensive haemorrhaging and perinatal death (Kostka
et al., 2001). The bleeding observed in this case was not due
to defective coagulation, but rather to abnormal EC morphology that included
hypertrophy, peculiar apical processes and increased intracellular vacuoles
(Kostka et al., 2001). In humans, a type of
synpolydactyly (congenital malformation of the hand) involves a chromosomal
translocation between the fibulin 1 gene and C12orf2 (Debeer et al., 2002). A haploinsufficiency in the
level of fibulin 1D is hypothesized to account for the limb abnormalities seen
(Debeer et al., 2002). In this regard,
mutation of fibrillin 2, a fibulin 1-associated protein (Visconti et al., 2003), also leads to syndactyly
(Chaudhry et al., 2001).
Several recent findings indicate the involvement of fibulins in
inherited eye disorders. Fibulins 1 and 4 are candidate genes for retinopathies
that map to chromosomes 22 and 11, respectively (Weigell-Weber et al., 2003). A mutation (Arg345Trp)
in the fibulin 3 gene has been linked to Malattia Leventinese (ML), a macular
dystrophy (Stone et al., 1999). During the
development of this disease, as well as in age-related macular degeneration
(AMD), an amorphous material known as drusen accumulates between the
retinal-pigment epithelium (RPE) and the Bruch's membrane. In ML, fibulin 3 is
not found in the drusen, but accumulates within cells of the RPE (Marmorstein et al., 2002). In AMD, which has no
associated fibulin 3 mutation, fibulin 3 nonetheless accumulates between the
RPE and the drusen (Marmorstein et al.,
2002). The expression of fibulins 3 and 1 are also elevated in a
murine retinopathy model that primarily involves degeneration of rod
photoreceptors (Kennan et al., 2002).
Ectopic expression of fibulin 1 also disrupts Xenopus eye morphogenesis
(Grammer et al., 2000).
Knockout experiments emphasize the essential role that fibulin 5 has
in elastic fibre assembly. Mice deficient in the expression of fibulin 5, an
elastin-binding protein, are viable but show symptoms of defective elastic
fibre formation, including a tortuous aorta, severe emphysema and loose skin
(cutis laxa; Nakamura et al., 2002;
Yanagisawa et al., 2002). In humans,
homozygosity for a missense mutation in fibulin 5 is also associated with a
severe form of cutis laxa (Loeys et al.,
2002) and a scarcity of elastic fibres.
Nematodes deficient in hemicentin (a homologue of fibulin 6) display
defective cell–cell and cell–matrix interactions (Vogel & Hedgecock, 2001). Uterine and intestinal cells
fail to affix stably to the body wall, and cells of the vas deferens fail to
join the cloaca. There is also a failure in the assembly of hemidesmosomes and
intermediate filaments in the epidermis.
Fibulins and cancer
Human fibrosarcoma tumour cell lines show a trend towards a
reduction or absence of fibulin 1D expression (Qing et
al., 1997). Fibrosarcoma cells that express fibulin 1D show
reduced growth in vivo, as well as a lowered growth capacity in soft
agar and a reduced ability to invade reconstituted basement membranes (Qing et al., 1997). Similarly, the ectopic
expression of fibulin 1D inhibits the motility of breast carcinoma cells on FN
(Twal et al., 2001). The motility
suppressive effects of fibulin 1D are attributed to a reduction in the cell
adhesion and migration-promoting activity of FN (Twal et
al., 2001). Ectopic expression of fibulin 1D also inhibits
transformation by the papillomavirus E6 gene (Du et
al., 2002). The mechanism by which fibulin 1D regulates
E6-mediated oncogenic activities might relate to the fact that these two
proteins interact (Du et al., 2002). These
findings support the conclusion that fibulin 1D acts as a tumour
suppressor.
Elevated expression of fibulin 1 is associated with human breast
tumours (Forti et al., 2002;
Greene et al., 2003). Also suggestive of
fibulin 1 overexpression in breast carcinoma is the fact that breast-cancer
patients produce antibodies against fibulin 1 (Forti et
al., 2002). These observations seem paradoxical in light of the
evidence that fibulin 1D is a tumour suppressor. An explanation may come from
findings that there is a trend towards increased expression of fibulin 1C
compared with the D variant in ovarian carcinomas (Moll
et al., 2002). Levels of fibulin 1 splice variants have not
been quantified in breast cancer but if fibulin 1C levels are elevated in
breast tumours as in ovarian tumours, it would suggest that fibulin 1C opposes
the action of fibulin 1D and promotes tumorigenesis. It is also possible that
humoral immunity to fibulin 1 in breast cancer reflects the breakdown of
fibulin 1D and concomitant loss of tumour suppression. In support of this,
increased levels of fibulin 1 fragments have been reported in human breast
tumours (Greene et al., 2003). Furthermore,
findings from DNA microarray studies of lung adenocarcinomas show that fibulins
1 and 2 are consistently associated with matrix metalloproteinase 2 expression,
a protein that promotes tumour invasion and metastasis (Creighton & Hanash, 2003).
Fibulin 2 has been identified as one of 64 overexpressed
metastasis-associated genes in solid tumours of diverse types (Ramaswamy et al., 2003). Fibulin 4 expression is
elevated in human colon tumours (Gallagher et al.,
2001), whereas cancers in other tissues tend to show downregulation
of fibulin 5 (Schiemann et al., 2002). In
contrast to the motility suppressive effects of fibulin 1D on fibrosarcoma
cells, overexpression of fibulin 5 increases fibrosarcoma cell migration
(Schiemann et al., 2002).
Fibulins in injury
The expression of several of the fibulins is induced in response to
injury. Fibulin 1 expression is increased in a murine model of cardiomyopathy
that is caused by increased Gi-receptor signalling (Redfern et al., 2000). In sun-damaged skin
elastosis, fibulin 2 deposition in association with elastic fibres is greatly
increased (Hunzelmann et al., 2001).
Fibulin 2 expression is also increased in the early phase of
streptozotocin-induced diabetic glomerulosclerosis (Wada
et al., 2001). In elastase-induced emphysema in mice, fibulin
5 expression is increased in the alveolar wall (Kuang et
al., 2003). The expression of fibulin 5, which is low in adult
arteries, is activated in medial and neointimal VSMCs in response to vascular
injury (Kowal et al., 1999), as well as in
lung vasculature in response to hyperoxia (Jean et
al., 2002) and in atherosclerotic plaques (Kowal et al., 1999). Transforming growth
factor- (TGF-), which has a key role in vascular injury response,
stimulates fibulin 5 expression (Schiemann et al.,
2002). Overexpression of fibulin 5 enhances basal and
TGF--mediated activation of p38 mitogen-activated protein kinase and
ERK1/ERK2 (Schiemann et al., 2002). A
similar profile of protein kinase activation has also been observed in response
to fibulin 1 stimuli (Twal et al., 2001).
Overexpression of fibulins 5 and 3 increase fibroblast DNA synthesis (Lecka-Czernik et al., 1996; Schiemann et al., 2002). Overexpression of fibulin 4
in macrophages also promotes DNA synthesis (Heine et
al., 1999), and fibulin 4 expression is augmented in macrophages
by lipopolysaccharide treatment, which suggests a role in response to sepsis
(Heine et al., 1999).
A recent study has shown that patients with unstable angina pectoris
and acute myocardial infarction have significantly reduced levels of plasma
fibulin 1 (Kawata et al., 2001). This has
led to speculation that plasma fibulin 1 may be transferred to or consumed in
or around the atherosclerotic lesion. Indeed, fibulin 1 is incorporated into
fibrin clots that are associated with atherosclerotic lesions (Tran et al., 1995). The significance of fibulin 1 in
the development of atherosclerosis is not yet known, but plasma fibulin 1 could
be important as a risk factor for cardiovascular diseases and atherosclerosis
progression.
Regulation of fibulin expression
Information is gradually emerging concerning the mechanisms that
regulate the expression of the fibulins during development or disease. Evidence
indicates that steroids regulate the expression of fibulins 1, 2 and 3.
Oestradiol stimulates fibulin 1C expression in ovarian tumour cells (Clinton et al., 1996; Hayashido
et al., 1998), and dexamethasone increases fibulin 1C
expression in human eye trabecular meshwork cells (Ishibashi
et al., 2002). Progesterone has been shown to stimulate the
expression of fibulins 1 and 2 in human endometrial stromal cells (Okada
et al., 2003). In a mouse Wilms' tumour model, the expression
of fibulin 2, but not fibulin 1, is increased by dexamethasone (Talts et al., 1995). Glucocorticoids downregulate
the expression of fibulins 1 and 2 in bone marrow stroma (Gu
et al., 2001) and oestrogen represses the expression of
fibulin 3 in MCF7 breast cancer cells (Hayashi et
al., 2003).
Sp transcription factors are important in fibulin 1 expression
(Castoldi & Chu, 2002; Grassel et al., 1999). Fibulin 1 transcription is
activated by the ubiquitous Sp1 and Sp3, but not by the more tissue-restricted
Sp4 (Castoldi & Chu, 2002). Fibulin 2 may be
similarly regulated (Grassel et al., 1999).
The fibulin 2 gene also contains two consensus cAMP-negative response elements.
Interaction of cAMP-activated liver X receptor- with these enhancer
elements results in increased fibulin 2 expression (Anderson
et al., 2003).
Future directions
The studies cited herein implicate the fibulins in an array of
physiological and pathological processes and open many new avenues for
investigation. For example, the finding that mutation of the fibulin 5 gene is
linked to cutis laxa highlights the possibility that mutations in genes
for the other family members might contribute to disorders that involve elastic
fibres. Given the circumstantial evidence that fibulin 1C and D variants might
have opposing effects on tumorigenesis, studies that directly test this
possibility and evaluate the expression of fibulin 1 variants in human tumours
are warranted. The finding that plasma fibulin 1 levels are reduced in coronary
heart disease patients raises questions as to the molecular basis for this and
whether this protein is a useful diagnostic serum marker. Just as our
understanding of the function of fibulins 1 and 5 has benefited from the study
of mice that are genetically deficient in the expression of these proteins,
similar benefit can be expected from the creation and study of mice that are
deficient in the other fibulin family members.
Supplementary
information is available at EMBO reports online
(http://www.emboreports.org).
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Acknowledgements
This work was supported by National Institutes of Health grant HL52813
(W.S.A.) and grants from the Irish Cancer Society, Enterprise Ireland, European
Commission and the Association for International Cancer Research (W.M.G.).
L.M.G. was supported by a PhD studentship from the Irish Cancer Society.
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References
Anderson, L.M., Choe, S.E., Yukhananov, R.Y., Hopfner, R.L., Church, G.M., Pratt, R.E. & Dzau, V.J. ( 2003) Identification of a novel set of genes regulated by a unique liver X receptor--mediated transcription mechanism. J. Biol. Chem., 278, 15252–15260. | Article | PubMed | ISI | ChemPort |
Argraves, W.S., Dickerson, K., Burgess, W.H. & Ruoslahti, E. ( 1989) Fibulin, a novel protein that interacts with the fibronectin receptor subunit cytoplasmic domain. Cell, 58, 623–629. | Article | PubMed | ISI | ChemPort |
Argraves, W.S., Tran, H., Burgess, W.H. & Dickerson, K. ( 1990) Fibulin is an extracellular matrix and plasma glycoprotein with repeated domain structure. J. Cell Biol., 111, 3155–3164. | Article | PubMed | ISI | ChemPort |
Bell, S.E., Mavila, A., Salazar, R., Bayless, K.J., Kanagala, S., Maxwell, S.A. & Davis, G.E. ( 2001) Differential gene expression during capillary morphogenesis in 3D collagen matrices: regulated expression of genes involved in basement membrane matrix assembly, cell cycle progression, cellular differentiation and G-protein signaling. J. Cell Sci., 114, 2755–2773. | PubMed | ISI | ChemPort |
Bouchey, D., Argraves, W.S. & Little, C.D. ( 1996) Fibulin-1, vitronectin, and fibronectin expression during avian cardiac valve and septa development. Anat. Rec., 244, 540–551. | Article | PubMed | ISI | ChemPort |
Castoldi, M. & Chu, M.L. ( 2002) Structural and functional characterization of the human and mouse fibulin-1 gene promoters: role of Sp1 and Sp3. Biochem. J., 362, 41–50. | Article | PubMed | ISI | ChemPort |
Chaudhry, S.S., Gazzard, J., Baldock, C., Dixon, J., Rock, M.J., Skinner, G.C., Steel, K.P., Kielty, C.M. & Dixon, M.J. ( 2001) Mutation of the gene encoding fibrillin-2 results in syndactyly in mice. Hum. Mol. Genet., 10, 835–843. | Article | PubMed | ISI | ChemPort |
Clinton, G.M., Rougeot, C., Derancourt, J., Roger, P., Defrenne, A., Godyna, S., Argraves, W.S. & Rochefort, H. ( 1996) Estrogens increase the expression of fibulin-1, an extracellular matrix protein secreted by human ovarian cancer cells. Proc. Natl Acad. Sci. USA, 93, 316–320. | Article | PubMed | ChemPort |
Creighton, C. & Hanash, S. ( 2003) Expression of matrix metalloproteinase 9 (MMP-9/gelatinase B) in adenocarcinomas strongly correlated with expression of immune response genes. In Silico Biol., 3, 0026 [epub ahead of print]. | PubMed |
Debeer, P., Schoenmakers, E.F., Twal, W.O., Argraves, W.S., De Smet, L., Fryns, J.P. & Van De Ven, W.J. ( 2002) The fibulin-1 gene (FBLN1) is disrupted in a t(12;22) associated with a complex type of synpolydactyly. J. Med. Genet., 39, 98–104. | Article | PubMed | ISI | ChemPort |
Du, M., Fan, X., Hong, E. & Chen, J.J. ( 2002) Interaction of oncogenic papillomavirus E6 proteins with fibulin-1. Biochem. Biophys. Res. Commun., 296, 962–969. | Article | PubMed | ISI | ChemPort |
Forti, S., Scanlan, M.J., Invernizzi, A., Castiglioni, F., Pupa, S., Agresti, R., Fontanelli, R., Morelli, D., Old, L.J., Pupa, S.M. & Menard, S. ( 2002) Identification of breast cancer-restricted antigens by antibody screening of SKBR3 cDNA library using a preselected patient's serum. Breast Cancer Res. Treat., 73, 245–256. | Article | PubMed | ISI |
Gallagher, W.M., Argentini, M., Sierra, V., Bracco, L., Debussche, L. & Conseiller, E. ( 1999) MBP1: a novel mutant p53-specific protein partner with oncogenic properties. Oncogene, 18, 3608–3616. | Article | PubMed | ISI | ChemPort |
Gallagher, W.M., Greene, L.M., Ryan, M.P., Sierra, V., Berger, A., Laurent-Puig, P. & Conseiller, E. ( 2001) Human fibulin-4: analysis of its biosynthetic processing and mRNA expression in normal and tumour tissues. FEBS Lett., 489, 59–66. | Article | PubMed | ISI | ChemPort |
Giltay, R., Timpl, R. & Kostka, G. ( 1999) Sequence, recombinant expression and tissue localization of two novel extracellular matrix proteins, fibulin-3 and fibulin-4. Matrix Biol., 18, 469–480. | Article | PubMed | ISI | ChemPort |
Grammer, T.C., Liu, K.J., Mariani, F.V. & Harland, R.M. ( 2000) Use of large-scale expression cloning screens in the Xenopus laevis tadpole to identify gene function. Dev. Biol., 228, 197–210. | Article | PubMed | ISI | ChemPort |
Grassel, S., Sicot, F.X., Gotta, S. & Chu, M.L. ( 1999) Mouse fibulin-2 gene. Complete exon–intron organization and promoter characterization. Eur. J. Biochem., 263, 471–477. | Article | PubMed | ISI | ChemPort |
Greene, L.M., Twal, W.O., Duffy, M.J., McDermott, E.W., Hill, A.D., O'Higgins, N.J., McCann, A.H., Dervan, P.A., Argraves, W.S. & Gallagher, W.M. ( 2003) Elevated expression and altered processing of fibulin-1 protein in human breast cancer. Br. J. Cancer., 88, 871–878. | Article | PubMed | ISI | ChemPort |
Gu, Y.C., Talts, J.F., Gullberg, D., Timpl, R. & Ekblom, M. ( 2001) Glucocorticoids down-regulate the extracellular matrix proteins fibronectin, fibulin-1 and fibulin-2 in bone marrow stroma. Eur. J. Haematol., 67, 176–184. | Article | PubMed | ISI | ChemPort |
Hayashi, S.I., Eguchi, H., Tanimoto, K., Yoshida, T., Omoto, Y., Inoue, A., Yoshida, N. & Yamaguchi, Y. ( 2003) The expression and function of estrogen receptor and in human breast cancer and its clinical application. Endocr. Relat. Cancer, 10, 193–202. | Article | PubMed | ISI | ChemPort |
Hayashido, Y., Lucas, A., Rougeot, C., Godyna, S., Argraves, W.S. & Rochefort, H. ( 1998) Estradiol and fibulin-1 inhibit motility of human ovarian- and breast-cancer cells induced by fibronectin. Int. J. Cancer, 75, 654–658. | Article | PubMed | ISI | ChemPort |
Heine, H., Delude, R.L., Monks, B.G., Espevik, T. & Golenbock, D.T. ( 1999) Bacterial lipopolysaccharide induces expression of the stress response genes hop and H411. J. Biol. Chem., 274, 21049–21055. | Article | PubMed | ISI | ChemPort |
Hungerford, J.E., Hoeffler, J.P., Bowers, C.W., Dahm, L.M., Falchetto, R., Shabanowitz, J., Hunt, D.F. & Little, C.D. ( 1997) Identification of a novel marker for primordial smooth muscle and its differential expression pattern in contractile vs noncontractile cells. J. Cell Biol., 137, 925–937. | Article | PubMed | ISI | ChemPort |
Hunzelmann, N., Nischt, R., Brenneisen, P., Eickert, A. & Krieg, T. ( 2001) Increased deposition of fibulin-2 in solar elastosis and its colocalization with elastic fibres. Br. J. Dermatol., 145, 217–222. | Article | PubMed | ISI | ChemPort |
Ishibashi, T., Takagi, Y., Mori, K., Naruse, S., Nishino, H., Yue, B.Y. & Kinoshita, S. ( 2002) cDNA microarray analysis of gene expression changes induced by dexamethasone in cultured human trabecular meshwork cells. Invest. Ophthalmol. Vis. Sci., 43, 3691–3697. | PubMed | ISI |
Jean, J.C., Eruchalu, I., Cao, Y.X. & Joyce-Brady, M. ( 2002) DANCE in developing and injured lung. Am. J. Physiol. Lung Cell Mol. Physiol., 282, L75–L82. | PubMed | ISI | ChemPort |
Kawata, K., Tanaka, A., Arai, M., Argraves, W.S. & Fukutake, K. ( 2001) Alteration of plasma fibulin-1 concentrations in ischemic heart diseases. Jpn. J. Thromb. Hemostasis, 12, 126–132. | ChemPort |
Kennan, A. et al. ( 2002) Identification of an IMPDH1 mutation in autosomal dominant retinitis pigmentosa (RP10) revealed following comparative microarray analysis of transcripts derived from retinas of wild-type and Rho(-/-) mice. Hum. Mol. Genet., 11, 547–557. | Article | PubMed | ISI | ChemPort |
Kluge, M., Mann, K., Dziadek, M. & Timpl, R. ( 1990) Characterization of a novel calcium-binding 90-kDa glycoprotein (BM-90) shared by basement membranes and serum. Eur. J. Biochem., 193, 651–659. | Article | PubMed | ISI | ChemPort |
Kostka, G., Giltay, R., Bloch, W., Addicks, K., Timpl, R., Fassler, R. & Chu, M.L. ( 2001) Perinatal lethality and endothelial cell abnormalities in several vessel compartments of fibulin-1-deficient mice. Mol. Cell. Biol., 21, 7025–7034. | Article | PubMed | ISI | ChemPort |
Kowal, R.C., Richardson, J.A., Miano, J.M. & Olson, E.N. ( 1999) EVEC, a novel epidermal growth factor-like repeat-containing protein upregulated in embryonic and diseased adult vasculature. Circ. Res., 84, 1166–1176. | PubMed | ISI | ChemPort |
Kuang, P.P., Goldstein, R.H., Liu, Y., Rishikof, D.C., Jean, J.C. & Joyce-Brady, M. ( 2003) Coordinate expression of fibulin-5/DANCE and elastin during lung injury repair. Am. J. Physiol. Lung Cell Mol. Physiol., 285, L1147–L1152. | PubMed | ISI | ChemPort |
Lecka-Czernik, B., Moerman, E.J., Jones, R.A. & Goldstein, S. ( 1996) Identification of gene sequences overexpressed in senescent and Werner syndrome human fibroblasts. Exp. Gerontol., 31, 159–174. | Article | PubMed | ChemPort |
Loeys, B., Van Maldergem, L., Mortier, G., Coucke, P., Gerniers, S., Naeyaert, J.M. & De Paepe, A. ( 2002) Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa. Hum. Mol. Genet., 11, 2113–2118. | Article | PubMed | ISI | ChemPort |
Mariani, T.J., Reed, J.J. & Shapiro, S.D. ( 2002) Expression profiling of the developing mouse lung: insights into the establishment of the extracellular matrix. Am. J. Respir. Cell Mol. Biol., 26, 541–548. | PubMed | ISI | ChemPort |
Marmorstein, L.Y., Munier, F.L., Arsenijevic, Y., Schorderet, D.F., McLaughlin, P.J., Chung, D., Traboulsi, E. & Marmorstein, A.D. ( 2002) Aberrant accumulation of EFEMP1 underlies drusen formation in Malattia Leventinese and age-related macular degeneration. Proc. Natl Acad. Sci. USA, 99, 13067–13072. | Article | PubMed | ChemPort |
Moll, F., Katsaros, D., Lazennec, G., Hellio, N., Roger, P., Giacalone, P.L., Chalbos, D., Maudelonde, T., Rochefort, H. & Pujol, P. ( 2002) Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells. Oncogene, 21, 1097–1107. | Article | PubMed | ISI | ChemPort |
Nakamura, T. et al. ( 1999) DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries. J. Biol. Chem., 274, 22476–22483. | Article | PubMed | ISI | ChemPort |
Nakamura, T. et al. ( 2002) Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature, 415, 171–175. | Article | PubMed | ISI | ChemPort |
Okada, H., Nakajima, T., Yoshimura, T., Yasuda, K. & Kanzaki, H. ( 2003) Microarray analysis of genes controlled by progesterone in human endometrial stromal cells in vitro. Gynecol. Endocrinol., 17, 271–280. | PubMed | ISI | ChemPort |
Pan, T.C., Sasaki, T., Zhang, R.Z., Fassler, R., Timpl, R. & Chu, M.L. ( 1993) Structure and expression of fibulin-2, a novel extracellular matrix protein with multiple EGF-like repeats and consensus motifs for calcium binding. J. Cell Biol., 123, 1269–1277. | Article | PubMed | ISI | ChemPort |
Qing, J., Maher, V.M., Tran, H., Argraves, W.S., Dunstan, R.W. & McCormick, J.J. ( 1997) Suppression of anchorage-independent growth and matrigel invasion and delayed tumor formation by elevated expression of fibulin-1D in human fibrosarcoma-derived cell lines. Oncogene, 15, 2159–2168. | Article | PubMed | ISI | ChemPort |
Ramaswamy, S., Ross, K.N., Lander, E.S. & Golub, T.R. ( 2003) A molecular signature of metastasis in primary solid tumors. Nature Genet., 33, 49–54. | Article | PubMed | ISI | ChemPort |
Redfern, C.H. et al. ( 2000) Conditional expression of a Gi-coupled receptor causes ventricular conduction delay and a lethal cardiomyopathy. Proc. Natl Acad. Sci. USA, 97, 4826–4831. | Article | PubMed | ChemPort |
Reinhardt, D.P., Sasaki, T., Dzamba, B.J., Keene, D.R., Chu, M.L., Gohring, W., Timpl, R. & Sakai, L.Y. ( 1996) Fibrillin-1 and fibulin-2 interact and are colocalized in some tissues. J. Biol. Chem., 271, 19489–19496. | Article | PubMed | ISI | ChemPort |
Roark, E.F., Keene, D.R., Haudenschild, C.C., Godyna, S., Little, C.D. & Argraves, W.S. ( 1995) The association of human fibulin-1 with elastic fibers: an immunohistological, ultrastructural, and RNA study. J. Histochem. Cytochem., 43, 401–411. | PubMed | ISI | ChemPort |
Sasaki, T., Gohring, W., Miosge, N., Abrams, W.R., Rosenbloom, J. & Timpl, R. ( 1999) Tropoelastin binding to fibulins, nidogen-2 and other extracellular matrix proteins. FEBS Lett., 460, 280–284. | Article | PubMed | ISI | ChemPort |
Schiemann, W.P., Blobe, G.C., Kalume, D.E., Pandey, A. & Lodish, H.F. ( 2002) Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor- and affects protein kinase cascades. J. Biol. Chem., 277, 27367–27377. | Article | PubMed | ISI | ChemPort |
Stone, E.M. et al. ( 1999) A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy. Nature Genet., 22, 199–202. | Article | PubMed | ISI | ChemPort |
Talts, J.F., Weller, A., Timpl, R., Ekblom, M. & Ekblom, P. ( 1995) Regulation of mesenchymal extracellular matrix protein synthesis by transforming growth factor- and glucocorticoids in tumor stroma. J. Cell Sci., 108, 2153–2162. | PubMed | ISI | ChemPort |
Timpl, R., Sasaki, T., Kostka, G. & Chu, M.L. ( 2003) Fibulins: a versatile family of extracellular matrix proteins. Nature Rev. Mol. Cell Biol., 4, 479–489. | Article | PubMed | ISI | ChemPort |
Tran, H., Tanaka, A., Litvinovich, S.V., Medved, L.V., Haudenschild, C.C. & Argraves, W.S. ( 1995) The interaction of fibulin-1 with fibrinogen. A potential role in hemostasis and thrombosis. J. Biol. Chem., 270, 19458–19464. | Article | PubMed | ISI | ChemPort |
Tran, H., Mattei, M., Godyna, S. & Argraves, W.S. ( 1997) Human fibulin-1D: molecular cloning, expression and similarity with S1-5 protein, a new member of the fibulin gene family. Matrix Biol., 15, 479–493. | Article | PubMed | ISI | ChemPort |
Tsuda, T., Wang, H., Timpl, R. & Chu, M.L. ( 2001) Fibulin-2 expression marks transformed mesenchymal cells in developing cardiac valves, aortic arch vessels, and coronary vessels. Dev. Dyn., 222, 89–100. | Article | PubMed | ISI | ChemPort |
Twal, W.O., Czirok, A., Hegedus, B., Knaak, C., Chintalapudi, M.R., Okagawa, H., Sugi, Y. & Argraves, W.S. ( 2001) Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility. J. Cell Sci., 114, 4587–4598. | PubMed | ISI | ChemPort |
Visconti, R.P., Barth, J.L., Keeley, F.W. & Little, C.D. ( 2003) Codistribution analysis of elastin and related fibrillar proteins in early vertebrate development. Matrix Biol., 22, 109–121. | Article | PubMed | ISI | ChemPort |
Vogel, B.E. & Hedgecock, E.M. ( 2001) Hemicentin, a conserved extracellular member of the immunoglobulin superfamily, organizes epithelial and other cell attachments into oriented line-shaped junctions. Development, 128, 883–894. | PubMed | ISI | ChemPort |
Wada, J., Zhang, H., Tsuchiyama, Y., Hiragushi, K., Hida, K., Shikata, K., Kanwar, Y.S. & Makino, H. ( 2001) Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis. Kidney Int., 59, 1363–1373. | Article | PubMed | ISI | ChemPort |
Weigell-Weber, M., Sarra, G.M., Kotzot, D., Sandkuijl, L., Messmer, E. & Hergersberg, M. ( 2003) Genomewide homozygosity mapping and molecular analysis of a candidate gene located on 22q13 (fibulin-1) in a previously undescribed vitreoretinal dystrophy. Arch. Ophthalmol., 121, 1184–1188. | Article | PubMed | ISI | ChemPort |
Yanagisawa, H., Davis, E.C., Starcher, B.C., Ouchi, T., Yanagisawa, M., Richardson, J.A. & Olson, E.N. ( 2002) Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo. Nature, 415, 168–171. | Article | PubMed | ISI |
Zhang, H.Y., Chu, M.L., Pan, T.C., Sasaki, T., Timpl, R. & Ekblom, P. ( 1995) Extracellular matrix protein fibulin-2 is expressed in the embryonic endocardial cushion tissue and is a prominent component of valves in adult heart. Dev. Biol., 167, 18–26. | Article | PubMed | ISI | ChemPort |
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