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Query: UMLS:C0036421 (PSS)
 10,989 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of fibronectin (FN), a major glycoproteic component of extra-cellular matrix, has been studies by an indirect immunofluorescence technique in the skin of 50 normal controls and 19 sclerodermic patients. In the normal skin, FN was present mainly in the papillary dermis, as thin strips and less abundant in reticular dermis, bound to collagen bundles. In scleroderma skins, FN was increased in the deep dermis of extensive and evolutive lesions (11 cases). In an other hand, the distribution of FN was not modified in stabilized lesions (8 cases). We conclude that the detection of FN in the scleroderma skin is an useful marker of the activity of the systemic sclerosis process and we discuss the possible role of FN as a primary matrix for organization of the collagenous connective tissue during the sclerosing process.
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PMID:[Distribution of fibronectin in the skin of patients with scleroderma]. 676 39

Scleroderma skin and the subcutaneous tissue was studied by indirect immunofluorescence with specific antibodies against interstitial collagens and procollagens, against fibronectin and against the basement membrane proteins Type IV collagen and laminin. Staining for Type I procollagen and fibronectin was distinctly increased in the lower dermis and subcutaneous tissue. When compared with normal skin the data suggests that fibrosis may start around capillaries and in close proximity to adipose cells. Additional changes in the distribution to Type IV collagen and laminin were found in some patients and probably reflect the alterations in small blood vessels.
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PMID:Immunofluorescence analysis of collagen, fibronectin, and basement membrane protein in scleroderma skin. 699 1

A hallmark of systemic sclerosis (SSc) is the development of tissue fibrosis. Excessive production of several connective tissue components normally present in the dermis, including type I, III, V, and VI collagens as well as fibronectin and proteoglycans, is a consistent finding in the skin of SSc patients. Type VII collagen is a major constituent of anchoring fibrils, present in the skin at the dermal-epidermal basement membrane zone. TGF-beta has been shown to upregulate the expression of the type VII collagen gene. In this study, we assessed the expression of type VII collagen and TGF-beta in the skin of patients with SSc. Indirect immunofluorescence showed an abundance of type VII collagen in the patients' skin, including the dermis. Ultrastructural analysis of SSc skin revealed an abundance of fibrillar material, possibly representing type VII collagen. The increased expression of type VII collagen epitopes was accompanied by the elevated expression of immunodetectable TGF-beta 1 and TGF-beta 2. Dermal fibroblasts cultured from the affected individuals showed a statistically significant (P < 0.02) increase in the expression of type VII collagen at the mRNA level, as detected by reverse transcription-PCR with a mutated cDNA as an internal standard, and increased deposition of the protein as assessed by indirect immunofluorescence. Thus, type VII collagen is abundantly present in SSc patients' dermis, a location not characteristic of its normal distribution, and its aberrant expression may relate to the presence of TGF-beta in the same topographic distribution. The presence of type VII collagen in the dermis may contribute to the tightly bound and indurated appearance of the affected skin in SSc patients.
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PMID:Elevated expression of type VII collagen in the skin of patients with systemic sclerosis. Regulation by transforming growth factor-beta. 751 91

In this study an amphotropic retrovirus has been used to efficiently transduce normal human (NF) and scleroderma (systemic sclerosis; SSc) dermal fibroblasts (SScF) with a sequence encoding a temperature-sensitive mutant of the SV40 large T antigen (tsA58-U19). From the primary outgrowths of skin explants, cultures were generated whose growth was stringently temperature-dependent. When grown at a low, permissive temperature (35 degrees C), both normal and SSc-transduced cells continuously divided with similar doubling times, whereas at a high, nonpermissive temperature (39.5 degrees C), division of both the NF and SScF cells was rapidly arrested. These cells have been passaged more than 50 times, have the typical morphological appearance of fibroblasts, and have retained an anchorage-dependent phenotype. The transduced normal cells (tsT-NF) synthesized the matrix molecules collagen and fibronectin and expressed phenotypic antigens characteristic of their nontransduced counterparts, including MHC Class I, VLA beta 1 (CD29), Hermes 1 (CD44), VLA-4 alpha (CD49d), ICAM-1 (CD54) and LFA-3 (CD58) and the cell surface ectoenzymes neutral endopeptidase (CD10), aminopeptidase N (CD13), and dipeptidyl peptidase IV (CD26). Analysis of the transduced SSc fibroblasts (tsT-SScF) showed that these cells exhibited certain major features of the SSc pathology, notably the abnormally high synthesis of type I collagen, increased expression of ICAM-1, and depressed levels of CD26. Moreover, these phenotypic characteristics were retained even after prolonged culture in vitro. The tsT-SScF cells also retained their responsiveness to cytokines, since interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) both produced a marked increase in ICAM-1 expression. Our findings show that infection of SScF with the SV40 tsT antigen extends the life span of these cells and does not ablate their abnormal phenotypic and functional characteristics.
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PMID:Scleroderma-derived human fibroblasts retain abnormal phenotypic and functional characteristics following retroviral transduction with the SV40 tsT antigen. 755 50

A hypothesis of the mechanism of systemic sclerosis associated impotence was developed by making a clinicopathological correlation between the results of preoperative erectile function testing and those of pathological examination of excised erectile tissue in an impotent man with systemic sclerosis. Preoperative examination revealed firm corporeal tissue with diminished penile stretch capability. Pharmacocavernosometry/pharmacocavernosography under conditions consistent with trabecular smooth muscle relaxation revealed severe diffuse corporeal veno-occlusive dysfunction. During penile implantation surgery the compact erectile tissue was unable to be dilated and required sharp corporeal tissue excision under direct vision to achieve cylinder insertion. Histological investigation of the excised corporeal tissue demonstrated severe corporeal fibrosis. Computer assisted color histomorphometry revealed that the mean percentage of trabecular smooth muscle area to total erectile tissue area was 18.2 +/- 13.9% (normal 40 to 52). Immunohistochemical staining with desmin, a protein found in smooth muscle, verified prolific corporeal fibrosis. In situ hybridization of the corporeal tissue demonstrated messenger ribonucleic acid collagen and fibronectin messenger ribonucleic acid expression. Strong hybridization signals were found in mesenchymal cell types, including trabecular smooth muscle cells. In summary, clinicopathological correlation revealed that veno-occlusive dysfunction and loss of penile length were secondary to the excessive accumulation of extracellular matrix, partially due to trabecular smooth muscle cells undergoing synthetic as opposed to contractile phenotypic activity.
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PMID:Systemic sclerosis and impotence: a clinicopathological correlation. 786 83

Recent studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha) selectively decreases production of collagens I and III, the major types of collagen in the dermis, and increases production of collagenase in cultured dermal fibroblasts. The effects of TNF-alpha on collagens I, III and VI, fibronectin and collagenase gene expression by fibroblasts derived from normal individuals and patients with systemic sclerosis (SSc) were studied. SSc is characterized by excessive accumulation of collagen in the skin and in certain organs. TNF-alpha inhibited collagen production and mRNA levels of collagens I and III and of fibronectin, and stimulated collagenase activity and collagenase mRNA levels in SSs fibroblasts. Levels of mRNA for alpha 1 (VI) and alpha 3 (VI) collagen and for beta-actin were unaltered in SSc fibroblasts incubated with TNF-alpha. Similar results were observed for mRNA levels in normal fibroblasts incubated with TNF-alpha. These results suggest that TNF-alpha could be expected to be beneficial in the treatment of SSc. In addition, our results indicated that collagen-VI expression is regulated independently from expression of collagens I and III, and expression of fibronectin and collagens I and III are regulated in parallel in fibroblasts treated with TNF-alpha.
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PMID:Effects of tumor necrosis factor-alpha on connective tissue metabolism in normal and scleroderma fibroblast cultures. 846 80

Activated fibroblasts were derived from the skin of patients with systemic scleroderma (SSc), used as a model for fibrosis. Such cells are characterized by increased production of collagens and other matrix constituents. Increased collagen and fibronectin production has been correlated with similarly elevated mRNA steady-state levels. In the present study we analysed the contribution of transcriptional activity and post-transcriptional transcript stability to the increases in pro-alpha 1(I) collagen and fibronectin mRNA steady-state levels in activated (scleroderma) fibroblasts. Fibroblasts, when cultured in close contact with a three-dimensional collagenous matrix, down-regulate collagen synthesis. Culture of skin fibroblasts from two patients with SSc in three-dimensional collagen lattices, however, showed 4-fold elevated pro-alpha 1(I) collagen mRNA levels over fibroblasts from healthy donors. Transcription of the COL1A1 gene in SSc fibroblasts was induced 2-3-fold over that in controls in both monolayer and lattice cultures, accounting in part for the elevated steady-state level. A 50% decrease in transcription rate in lattice compared with monolayer culture occurred, as in control cells. In contrast, whereas control cells in lattices responded with decreased (50%) pro-alpha 1(I) collagen mRNA stability, in SSc cells these transcripts were found to be more stable (half-life of 5 h compared with 2 h in control cells). Fibronectin steady-state mRNA levels, in contrast, were not significantly regulated by the three-dimensional environment. In SSc fibroblasts, fibronectin mRNA levels were induced 1.5-4.9-fold over controls. In part, this increase appears to be due to elevated transcription, and an increase in fibronectin transcript stability was also detected. We therefore conclude that activated fibroblasts such as those derived from scleroderma patients utilize transcriptional and posttranscriptional mechanisms to maintain increased collagen and fibronectin production, which contribute to the pathogenesis of the disease.
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PMID:Differential regulation of transcription and transcript stability of pro-alpha 1(I) collagen and fibronectin in activated fibroblasts derived from patients with systemic scleroderma. 861 28

Interstitial pulmonary fibrosis in developing countries is now diagnosed with an increased frequency. Increased awareness and more frequent availability of computed tomography and fiberoptic bronchoendoscopy have helped in making the diagnosis more often. The spectrum of diseases causing pulmonary fibrosis is broadly similar to that seen in the West. Connective tissue disorders such as systemic sclerosis and rheumatoid arthritis and sarcoidosis are more common causes. Idiopathic fibrosis is seen in approximately half the patients. Pneumoconiosis such as silicosis are also important. Diagnosis is often established on the basis of clinical features and radiologic findings alone. Transbronchial lung biopsy is used as a frequent method to make histologic diagnosis. Some of the causes described from India are rather rare. One of the interesting examples included a patient in whom pulmonary fibrosis was related to his ascent to very high altitude. Extreme cold, solar radiation, and other factors complicating low atmospheric oxygen pressure were implicated as causative factors. Lung fibrosis, secondary to exposure to toxic gas (methyl isocyanate), is reported in survivors of the Bhopal gas leakage tragedy of 1984. Serial bronchoalveolar studies have show elevated fibronectin levels and the presence of macrophage-neutrophilic exudate in the lavage fluid.
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PMID:Incidence and recognition of interstitial pulmonary fibrosis in developing countries. 933 41

Systemic sclerosis (SSc) is a multisystem connective tissue disorder in which there is progressive fibrosis. Transforming growth factor beta (TGF beta) has wide-ranging cellular actions. It is a potent chemoattractant for human dermal fibroblasts, from which it may induce synthesis of collagen, which suggests that it may have a central role to play in the pathogenesis of SSc. This is supported to some extent by in vitro studies. SSc fibroblasts produce more collagens and fibronectin than normal fibroblasts and elevated TIMP levels have been observed, all of which could be explained on the basis of TGF beta stimulation of fibroblasts. Some studies have suggested that fibroblasts are the source of TGF beta. However, the serum of patients with SSc is cytotoxic to endothelial cells, which could culminate in TGF beta synthesis by them, with secondary fibroblast stimulation. The role of TGF beta remains elusive, although it would seem an ideal candidate as a mediator of fibrosis in systemic sclerosis.
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PMID:TGF beta--a role in systemic sclerosis? 958 19

Systemic sclerosis (SSc), a multisystem immunologic disease of unknown etiology, is commonly manifested in the lung as fibrosing alveolitis (FASSc). There is evidence to support the role of genetic factors in the predisposition to pulmonary fibrosis in SSc (HLA DR3/DR52a). This association is not complete and other candidate genes are likely involved. Of these, fibronectin is a growth factor known to play a crucial role in lung fibrosis. Our study investigated whether polymorphisms of the fibronectin gene are associated with lung fibrosis in SSc. Using the polymerase chain reaction and the restriction enzymes HaeIII, MspI, HindIII, and TaqI, we assessed the restriction fragment length polymorphisms (RFLPs) in 161 patients with SSc and 253 healthy control subjects from the United Kingdom. For each restriction enzyme, three genotypes were possible corresponding to the presence of the cutting site on neither, one, or both chromosomes (HaeIII AA, AB, BB; MspI CC, CD, DD; HindIII EE, EF, FF; TaqI GG, GH, HH). There was a significant decrease of genotype BB (FASSc: 17%, control: 34%; Pcorr = 0.006) with a reciprocal increase of genotype AB (FASSc: 62%, control: 46%; Pcorr = 0.022) in FASSc with the HaeIII RFLP. A significant decrease of genotype DD was observed in FASSc (FASSc: 28%, control: 41%; Pcorr = 0.038) with the MspI RFLP. The coassociation of genotypes AB (HaeIII RFLP) and CD (MspI RFLP) was present in 45% of the FASSc group (P = 0.0059), with an increased relative risk of developing fibrosing alveolitis of 1.988. We conclude that genotypes of the fibronectin gene are useful prognostic factors in SSc, helping to predict individuals likely to develop pulmonary fibrosis.
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PMID:Fibronectin gene polymorphisms associated with fibrosing alveolitis in systemic sclerosis. 987 Sep 23


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