Increase in fibronectin in the deep dermis of involved skin in progressive systemic sclerosis

Cooper, Sheldon M.; Keyser, Anthony J.; Beaulieu, André; Ruoslahti, Erkki; Nimni, Marcel E.; Quismorio, Francisco P.

doi:10.1002/art.1780220906

Cited by 74 publications

(14 citation statements)

References 18 publications

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“…A similar distribution of total fibronectin has also been observed in dcSSc skin [40]. The significance of this is unclear, however, it may reflect microenvironmental differences between the papillary and reticular dermis or the existence of heterogeneous fibroblast populations within the respective dermal compartments, or a combination of both these factors.…”

Section: Discussionsupporting

confidence: 68%

Shared expression of phenotypic markers in systemic sclerosis indicates a convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis

et al. 2005

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The mechanisms by which microvascular damage leads to dermal fibrosis in diffuse cutaneous systemic sclerosis (dcSSc) are unclear. We hypothesized that microvascular pericytes constitute a cellular link between microvascular damage and fibrosis by transdifferentiating into myofibroblasts. We used a combination of immunohistochemistry and double immunofluorescence labelling of frozen skin biopsies taken from normal and dcSSc patients to determine whether a phenotypic link between pericytes and myofibroblasts exists in dcSSc. Using α-smooth muscle actin, the ED-A splice variant of fibronectin (ED-A FN) and Thy-1 to identify myofibroblasts, we demonstrated the presence of myofibroblasts in fibrotic dcSSc skin. Myofibroblasts were totally absent from control skin, atrophic stage dcSSc skin and non-lesional skin. Using double immunofluorescence labelling, both myofibroblasts and pericytes were shown to express ED-A FN and Thy-1 in dcSSc skin but not in control skin. Proliferating cell nuclear antigen was also expressed by myofibroblasts and pericytes in dcSSc skin while being absent in control skin. These observations suggest that the presence of myofibroblasts may represent a transitional phase during the fibrotic stages of dcSSc and that Thy-1 +ve pericytes participate in the fibrogenic development of dcSSc by synthesizing ED-A FN, which may be associated with a proliferation and transition of pericytes and fibroblasts to myofibroblasts, thus linking microvascular damage and fibrosis.

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Section: Discussionsupporting

confidence: 68%

Shared expression of phenotypic markers in systemic sclerosis indicates a convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis

et al. 2005

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“…The difference from our results may by due to improved sensitivity of our antibody and it may be that we also obtained deeper biopsies. A similar increase in deep dermal fibronectin expression has also been previously reported in scleroderma [34, 35]. Further work is required to establish whether the altered expression of fibronectin in lichen sclerosus is a consequence of altered rates of its synthesis and/or degradation by proteases.…”

Section: Discussionmentioning

confidence: 60%

Alterations in Distribution of Tenascin, Fibronectin and Fibrinogen in Vulval Lichen sclerosus

Farrell¹,

Dean²,

Charnock³

et al. 2000

Dermatology

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Background: The pathophysiology of lichen sclerosus remains uncertain. The clinical features, including increased fragility and scarring, and the histology suggest that significant reorganisation of the extracellular matrix is occurring. Tenascin, fibrinogen and fibronectin are extracellular matrix components that play a significant role in tissue remodelling, for example during wound repair. Aim: To examine the distribution of tenascin, fibrinogen and fibronectin in vulval lichen sclerosus. Materials and Methods: Immunohistochemical staining was performed to study the distribution of tenascin, fibronectin and fibrinogen in 16 specimens of untreated vulval lichen sclerosus and 1 specimen of extragenital lichen sclerosus. Haematoxylin and eosin staining of the specimens was also performed to identify the position of the pale staining homogenous zone/zone of sclerosis and the inflammatory infiltrate below this. The control tissues studied included biopsies taken from the uninvolved thigh of 13 of the lichen sclerosus patients and 6 samples of normal vulva tissue obtained during gynaecological procedures from women of similar age to the lichen sclerosus women. Results: All the lichen sclerosus specimens demonstrated increased immunostaining of tenascin in the upper dermis and comparing this with the haematoxylin and eosin staining this corresponded to the zone of sclerosis with relatively little tenascin staining associated with the inflammatory band. In 14 out of the 16 vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen fibrinogen immunostaining was increased in the upper dermis which corresponded – in haematoxylin and eosin staining – to the zone of sclerosis. There was also slightly increased fibrinogen staining in the mid dermis which corresponded to the inflammatory band. Fibronectin staining was reduced in the upper dermis of 12 of the vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen which corresponded to the zone of sclerosis. However, in 14 of the vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen, fibronectin was slightly increased in the mid and deeper dermis which corresponded to the zone of inflammatory cells and the area below this. There was also increased fibronectin staining around blood vessel walls both in the mid dermis and within the zone of sclerosis. Conclusion: The distribution of tenascin, fibrinogen and fibronectin is altered in lichen sclerosus and the alteration in these extracellular matrix components may be relevant to the initiation of scarring in lichen sclerosus and the associated increased skin fragility.

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“…The last substance has been reported to play an important role in the removal of collagenous particles, fibrin and cell debris via sessile macrophages of the reticuloendothelial system (44,45). Recently, abnormally high levels of fibronectin have been demonstrated in the dermis of involved skin in progressive systemic sclerosis (46). Fibronectin is also found in the circulation of normal humans at a concentration of 300-400 pg/ml (47).…”

Section: Discussionmentioning

confidence: 99%

Dna in synovial fluid and the circulation of patients with arthritis

Leon

Revach²,

Ehrlich

et al. 1981

Arthritis & Rheumatism

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DNA levels were measured in synovial fluids and sera of 106 patients with rheumatoid arthritis (RA), osteoarthritis (OA), gout, pseudogout, and posttraumatic arthritis (TRA). In synovial fluids, the highest concentration was found in rheumatoid arthritis (mean f SE 18 f 3 pg/d for seropositive and 9 f 1 pg/d for seronegative variants), gout and pseudogout (17 f 3 pg/ ml). In contrast, the levels in patients with OA or acute TRA were very low: 0.8 f 0.1 pg/d and 1.1 f 0.2 pg/ ml, respectively. The difference between the means of the first disease group and OA or TRA is statistically significant. A similar pattern was observed for DNA levels in the circulation: in rheumatoid arthritis, the mean concentration was 135 f 28 ng/ml and 164 f 39 n g / d for seropositive and seronegative RA, respectively. Again the levels in OA and TRA were much lower, 52 k 18 ng/ml and 0 ng/ml, respectively. The latter are not significantly different from the mean levels of 95 normal,

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Increase in fibronectin in the deep dermis of involved skin in progressive systemic sclerosis

Cited by 74 publications

References 18 publications

Shared expression of phenotypic markers in systemic sclerosis indicates a convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis

Shared expression of phenotypic markers in systemic sclerosis indicates a convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis

Alterations in Distribution of Tenascin, Fibronectin and Fibrinogen in Vulval Lichen sclerosus

Dna in synovial fluid and the circulation of patients with arthritis

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