Fibrillin-1 and Fibulin-2 Interact and Are Colocalized in Some Tissues

Reinhardt, Dieter P.; Sasaki, Takako; Dzamba, Bette J.; Keene, Douglas R.; Chu, Mon Li; Göhring, Walter; Timpl, Rupert; Sakai, Lynn Y.

doi:10.1074/jbc.271.32.19489

Cited by 206 publications

(227 citation statements)

References 44 publications

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“…Cells were washed with Tris buffered saline (TBS; 50 mM Tris [pH 8.0], 150 mM NaCl) and then incubated with rabbit antifibrillin antibody (pAb9543; kindly provided by Dr. Lynn Sakai [17,24]) at 1:250 dilution in TBS for 2 hours at 37°C. This antibody was raised against the amino-terminal half of human fibrillin-1 and cross-reacts with mouse fibrillin-1, but not with fibrillin-2 (17,24). Some cells were also incubated with mouse monoclonal anti-␣-smooth muscle actin (anti-␣-SMA) antibodies (clone 1A4; Sigma, St. Louis, MO) at a 1:250 dilution in TBS during the same time period.…”

Section: Methodsmentioning

confidence: 99%

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Transforming growth factor β induces fibroblast fibrillin‐1 matrix formation

Kissin¹,

Lemaire²,

Korn³

et al. 2002

Arthritis & Rheumatism

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Objective. Fibrillin, an extracellular matrix protein implicated in dermal fibrosis, is increased in the reticular dermis of systemic sclerosis (SSc) skin. We undertook this study to investigate the hypothesis that transforming growth factor ␤ (TGF␤) or other cytokines regulate fibrillin matrix formation by normal and SSc fibroblasts. We further investigated the mechanism of TGF␤-induced fibrillin fibrillogenesis and its relationship to myofibroblasts.Methods. Fibrillin and fibronectin matrix deposition and ␣-smooth muscle actin expression by fibroblast cultures from normal and SSc skin treated with TGF␤ or other cytokines were analyzed by immunofluorescence. Supernatant and extracellular matrix from normal and SSc fibroblasts treated with or without TGF␤ were evaluated by Western blot and Northern blot for fibrillin protein and messenger RNA (mRNA) expression, respectively.Results. Immunofluorescence demonstrated increased fibrillin matrix formation by normal and scleroderma fibroblasts after TGF␤ treatment. Other cytokines, including tumor necrosis factor ␣, interleukin-1␤ (IL-1␤), IL-4, granulocyte-macrophage colonystimulating factor, and platelet-derived growth factor, did not affect fibrillin fibrillogenesis. Fibrillin matrix formed in proximity to myofibroblasts and independently of up-regulation of fibronectin matrix or cell number. Western blot analysis of extracellular matrix confirmed increased fibrillin after TGF␤ stimulation of normal or scleroderma fibroblasts. However, TGF␤ did not alter the expression of either soluble fibrillin protein or fibrillin mRNA.Conclusion. Our data show that TGF␤ induces fibrillin protein incorporation into the extracellular matrix without affecting fibrillin gene expression or protein synthesis, suggesting that fibrillin matrix assembly is regulated extracellularly. TGF␤ might increase fibrillin matrix by activating myofibroblasts. Such TGF␤-mediated effects could account for the increased fibrillin matrix observed in SSc skin.

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Section: Methodsmentioning

confidence: 99%

“…Fibrillin-containing microfibrils interact both with basement membranes and with nearby elastic fibers and may help stabilize the extracellular matrix by forming a scaffold (17).…”

mentioning

confidence: 99%

Transforming growth factor β induces fibroblast fibrillin‐1 matrix formation

Kissin¹,

Lemaire²,

Korn³

et al. 2002

Arthritis & Rheumatism

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“…Whilst the supra-molecular conformation of fibrillin within the microfibril remains a matter of debate, with published experimental evidence favouring both 1/3 staggered (Downing et al 1996;Lee et al 2004) and hinged arrangements (Baldock et al 2001;Kielty et al 2005), it appears clear that, in the mature microfibril, an average of eight processed monomers are present within each repeat (Baldock et al 2001;Sherratt et al 1997). It is likely that interactions of fibrillin-1 with itself and with MAGP-1, tropoelastin and fibulin-2, as demonstrated in vitro, play a central role in elastogenesis and elastic fibre function in vivo (Jensen et al 2001;Kielty et al 2005;Reinhardt et al 1996;Rock et al 2004;Tiedemann et al 2001). In addition to mediating matrix/matrix interactions, a Assembly of fibrillin into microfibrils and the association of microfibrils with tropoelastin to form elastic fibres is a highly organised process which is limited to foetal and early neonatal development.…”

Section: Structure and Functionmentioning

confidence: 99%

“…As with the LTBPs, their structure is based in contiguous cbEGF domains and three of the five fibulins (fibulin-1, -2 and -5) are known to be elastic fibre components (Kielty et al 2002). Fibulin-1 is primarily localised to the elastin core (Kostka et al 2001) whilst fibulin-2 and -5 are located at the microfibril/elastin interface (Nakamura et al 2002;Reinhardt et al 1996).…”

Section: Structure and Functionmentioning

confidence: 99%

Tissue elasticity and the ageing elastic fibre

Sherratt

2009

AGE

265

189

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The ability of elastic tissues to deform under physiological forces and to subsequently release stored energy to drive passive recoil is vital to the function of many dynamic tissues. Within vertebrates, elastic fibres allow arteries and lungs to expand and contract, thus controlling variations in blood pressure and returning the pulmonary system to a resting state. Elastic fibres are composite structures composed of a cross-linked elastin core and an outer layer of fibrillin microfibrils. These two components perform distinct roles; elastin stores energy and drives passive recoil, whilst fibrillin microfibrils direct elastogenesis, mediate cell signalling, maintain tissue homeostasis via TGFβ sequestration and potentially act to reinforce the elastic fibre. In many tissues reduced elasticity, as a result of compromised elastic fibre function, becomes increasingly prevalent with age and contributes significantly to the burden of human morbidity and mortality. This review considers how the unique molecular structure, tissue distribution and longevity of elastic fibres pre-disposes these abundant extracellular matrix structures to the accumulation of damage in ageing dermal, pulmonary and vascular tissues. As compromised elasticity is a common feature of ageing dynamic tissues, the development of strategies to prevent, limit or reverse this loss of function will play a key role in reducing age-related morbidity and mortality.

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“…This might be especially important for papillary carcinoma which exhibits a high degree of elastosis, 17 inasmuch as fibrillin-1 has been suggested to be colocalized with elastin in various tissues. 8,18 Although the mechanism of fibrillin-1 deposition in ECM is largely unknown, it has been shown that in epithelial cells, soluble heparin competitively inhibits an unknown interaction that is needed for ECM deposition of both fibrillin-1 and -2. 13 Moreover, a human fibrillin-1 mutation (Arg 2726 -Trp) which prevents proteolytic processing of the C-terminal domain, has been reported to result in impaired deposition of the product of the affected allele.…”

Section: Discussionmentioning

confidence: 99%

Fibrillin expression and localization in various types of carcinomas of the thyroid gland

et al. 2006

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Fibrillin is an extracellular matrix (ECM) glycoprotein, a main component of microfibrills, suggested to support cell attachment and to impact cell differentiation and migration. The aim of this study was to investigate fibrillin-1 expression in thyroid carcinomas at mRNA and protein level, since ECM proteins are suggested to be of great importance for the metastatic potential of carcinomas. RNA was extracted from 13 thyroid carcinoma cell lines and RT-PCR analysis with gene-specific primers revealed fibrillin-1 mRNA expression in all cell lines, with highest expression in the follicular carcinoma cell line WRO and lowest expression in the two anaplastic cell lines (APO, FRO). Furthermore, we investigated fibrillin-1 expression by immumohistochemistry in a commercially available tissue microarray including 50 thyroid carcinomas as well as in archival tissue from 33 thyroid carcinomas. Fibrillin-1 demonstrated a cytoplasmic location in the neoplastic cells of almost all carcinomas apart from the follicular ones. The most intense staining was observed in papillary carcinomas with some evidence of a slight increased intensity in advanced stages. Our data indicate that fibrillin-1 is strongly expressed by the neoplastic cells of thyroid carcinomas in different degree in the various histologic types and might be implicated in cell-stroma interaction in terms of signaling, attachment and migration.

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Fibrillin-1 and Fibulin-2 Interact and Are Colocalized in Some Tissues

Cited by 206 publications

References 44 publications

Transforming growth factor β induces fibroblast fibrillin‐1 matrix formation

Transforming growth factor β induces fibroblast fibrillin‐1 matrix formation

Tissue elasticity and the ageing elastic fibre

Fibrillin expression and localization in various types of carcinomas of the thyroid gland

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