UMLS:C0034069 - FACTA Search

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Query: UMLS:C0034069 (pulmonary fibrosis)
7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a 52-years-old female patient with collagen disease and pulmonary hypertension. Denopamine, beta-adrenergic agonist, decreased her high pulmonary arterial pressure and improved dyspnea on exercise after long term use. She had suffered from Raynaud's phenomenon, pulmonary fibrosis, shortening of lingual frenulum and positive ANA and RA test. Although her pulmonary fibrosis had been well controlled by azathioprine, dyspnea on exercise became worse, so she admitted to our hospital for further examination in Feb 1988. Right heart catheterization revealed her high pulmonary arterial pressure (mean 29 mmHg). Under right heart catheterization, denopamine markedly decreased her pulmonary arterial pressure and increased her cardiac output. After about 6 weeks' use of denopamine, her mean pulmonary arterial pressure decreased to 15 mmHg, PO2 increased from 43 to 62 mmHg and dyspnea improved. Denopamine has been regarded as a selective beta 1-adrenergic agonist. In this case, denopamine might have beta 2-agonist effect to dilate pulmonary vasculature, or have secondary effect to increase PO2 by the improvement of cardiac function. Denopamine might be useful for pulmonary hypertension with collagen diseases.
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PMID:[Denopamine responsive pulmonary hypertension in a patient with collagen disease]. 257 12

Evidence suggests that transforming growth factor beta (TGF-beta) may play a central role in a variety of fibroproliferative disorders via the induction of extracellular matrix accumulation. The three mammalian TGF-beta isoforms are present in the normal lung, but very little is known about their expression during lung injury and repair. To more fully understand the role of TGF-beta in lung repair, we investigated the expression of the TGF-beta 1, TGF-beta 2, and TGF-beta 3 isoforms in a bleomycin-induced model of pulmonary fibrosis using immunohistochemical and in situ hybridization techniques. We found expression of the three TGF-beta isoforms, in an identical pattern, widely distributed throughout the normal rat lung: in airways, blood vessels, lung parenchyma, and alveolar macrophages. In general, the distribution of TGF-beta mRNA and protein coincided; however, bronchial epithelial cells were a notable exception, exhibiting immunoreactivity but no mRNA expression. During the "inflammatory" phase (days 1 and 3) of bleomycin-induced injury there was an increase in the mRNA and protein expression of all three TGF-beta isoforms in the injured areas, most prominently in parenchymal cells and alveolar macrophages. There was a further increase in TGF-beta isoform expression in the areas of developing fibrosis during the later reparative phase (days 7 and 14), and the bronchial epithelium, previously not expressing TGF-beta mRNA, showed strong expression of mRNA for the three isoforms concomitant with increased immunoreactivity. These findings implicate the three mammalian TGF-beta isoforms in the dysregulated repair process that results in pulmonary fibrosis. Furthermore, the pattern of TGF-beta mRNA and protein expression by the bronchial epithelium suggests that a transition may occur at this site from a paracrine mode of action in the normal lung to an autocrine mode of action during the "reparative" phase of fibrosis.
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PMID:Increased expression of transforming growth factor beta isoforms (beta 1, beta 2, beta 3) in bleomycin-induced pulmonary fibrosis. 754 Dec 21

Transforming growth factor-beta (TGF-beta) and interleukin-1 (IL-1) are essential participants in the development of pulmonary fibrosis. Administration of inhibitors to either cytokine can prevent the onset and progression of lung fibrosis in animal models. In this report, stable Thy-1+ and Thy-1- murine lung fibroblast subpopulations were analyzed for expression of the three mammalian TGF-beta isoforms. TGF-beta 1, TGF-beta 2, and TGF-beta 3 mRNA transcripts were detected by reverse transcriptase-PCR in both murine fibroblast subsets. Most of the TGF-beta produced by fibroblasts is latent; however, a small amount of active TGF-beta can be detected using a sensitive mink lung cell bioassay. By incorporating neutralizing anti-TGF-beta isoform-specific antibodies, it was determined that TGF-beta 1 is the predominant isoform present in both the active and the latent forms. Overall, Thy-1- fibroblasts secrete twice as much latent TGF-beta as the Thy-1+ subset. To investigate whether a link exists between TGF-beta and IL-1, the effect of TGF-beta 1 on the expression of IL-1 receptor type I (IL-1RtI) by fibroblast subsets was assessed by flow cytometry and Scatchard analysis. TGF-beta 1 significantly down-regulates the expression of IL-1RtI by Thy-1+ fibroblasts, but not by Thy-1- fibroblasts. A functional consequence of this down-regulation of the IL-1RtI is that it makes Thy-1+ fibroblasts less responsive to IL-1-mediated induction of IL-6 protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of TGF-beta isoforms by Thy-1+ and Thy-1- pulmonary fibroblast subsets: evidence for TGF-beta as a regulator of IL-1-dependent stimulation of IL-6. 785 60

Sarcoidosis is a chronic inflammatory disease of unknown cause characterized by the formation of nonnecrotizing granulomas in affected tissues, most notably the lungs. Granuloma healing may result in pulmonary fibrosis and respiratory impairment in some patients. Transforming growth factor-beta 1 (TGF-beta 1) is a potent cytokine that promotes fibrosis by enhancing the synthesis of extracellular matrix components, including fibronectin and the alpha 5 beta 1 fibronectin receptor. The role of TGF-beta 1 in promoting lung fibrosis in the setting of pulmonary sarcoidosis has not yet been investigated. Accordingly, we determined the extent and distribution of TGF-beta 1 in lung tissue obtained from seven patients with clinical and histologic features of pulmonary sarcoidosis. The tissue distributions of TGF-beta 1, the TGF-beta 1 binding proteoglycan decorin, fibronectin, and the alpha 5 beta 1 fibronectin receptor were assessed immunohistochemically. In all cases, the epithelioid histiocytes comprising nonnecrotizing granulomas of pulmonary sarcoidosis contained abundant TGF-beta 1. We further demonstrated decorin, fibronectin, and the alpha 5 beta 1 fibronectin receptor within nonnecrotizing granulomas and in the fibrous tissue surrounding the lesions. TGF-beta 1 staining was also observed in bronchiolar epithelial cells, hyperplastic Type II pneumocytes, and occasional alveolar macrophages. This study demonstrates enhanced tissue localization of TGF-beta 1 and related extracellular matrix proteins associated with the nonnecrotizing granulomas of pulmonary sarcoidosis. Through its actions on matrix protein synthesis, TGF-beta 1 may modulate the fibrotic repair process accompanying granuloma healing in sarcoidosis.
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PMID:Immunohistochemical localization of transforming growth factor-beta 1 in the nonnecrotizing granulomas of pulmonary sarcoidosis. 811 83

Cell-mediated contraction of tissues containing fibrillar collagens can lead to organ compromise and loss of function. The same process that is biologically advantageous during the contraction phase of wound healing can be subverted in diseases such as hepatic cirrhosis, pulmonary fibrosis, and scleroderma, although the cellular and molecular mechanism of matrix tissue contraction is difficult to study in such chronic diseases. However, certain human eye diseases that result in tractional detachment of the retina and loss of vision are characterized by acute cell-mediated contraction of collagenous tissue in the vitreous cavity. In this study, we demonstrate that human cells can contract vitreous, a complex biological gel containing type II collagen, in vitro. This cell-mediated contraction can be blocked by antibodies and peptides that antagonize the function of alpha 2 beta 1 integrin, and the potential for contraction can be conferred upon noncontracting cells by stable transfection of cells with alpha 2 cDNA. We also show that this contractile process, if focally resisted, can result in remodeling vitreous from a gel to a structure that resembles a planar membrane, and that substantial isometric forces can be measured across this tissue. We propose that in diseases such as proliferative diabetic retinopathy and proliferative vitreoretinopathy, alpha 2 beta 1 integrin-mediated contraction of the vitreous and tension at the site of vitreoretinal attachments contribute to the terminal event of tractional retinal detachment. By extension, we propose that alpha 2 beta 1 integrin is a centrally important molecule in human diseases characterized by remodeling and contraction of collagenous tissue (i.e., fibrocontractive diseases).
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PMID:A potential pathophysiologic role for alpha 2 beta 1 integrin in human eye diseases involving vitreoretinal traction. 822 12

Hepatic silicosis, cirrhosis, liver cell adenoma, and carcinomas developed in nude mice (NCr-Nu) given quartz by the subcutaneous and intraperitoneal routes. Syrian golden hamsters (15:16 EHS:cr) given quartz by both routes developed extensive fibrosis and cirrhosis and had higher morbidity and mortality rates after 3 months. Crystalline silica (quartz) induces fibrosis, adenomas, and carcinomas in the lungs of Fisher 344 rats, but certain strains of mice and hamsters are resistant to quartz-induced pulmonary carcinogenesis. Pulmonary fibrosis, however, is minimal in mice and absent in hamsters who received quartz intratracheally. To determine whether species differences are due to organ-specific rather than species-specific factors, susceptibility of the liver to quartz toxicity was investigated in nude mice and hamsters. The present study shows that the differential manifestations of quartz toxicity by these rodent species are dependent on factors that are organ-specific rather than host-specific. At 3 months, hepatocytes in mice were immunostained with intracellular transforming growth factor (TGF) beta 1 (LC 1-30) but not with TGF-beta 1 latency-associated peptide (LAP) protein (266-278); at 12 months, hepatocytes were immunostained with TGF-beta 1 LAP (266-278) but not with TGF-beta 1 (LC1-30). The hepatocytes of hamsters at 3 months showed immunoreactivities to TGF-beta 1 LAP (266-278) and TGF-beta 1 (LC1-30); immunostaining to TGF-beta 1 (LC1-30) was detected in nonparenchymal cells. Extracellular TGF-beta 1 (CC1-30) was detected in the silicotic granulomas and fibrous tissue in livers of both species. Quartz-induced liver carcinoma did not express TGF-beta 1 LAP (266-278) and LC (1-30) proteins, but these were detected in the cells of the adenoma in the same liver. Control animals showed no hepatic lesions nor immunoreactivity to TGF-beta 1. The spatial and temporal patterns of expression of TGF-beta 1, TGF-beta 2, TGF-beta receptor type II messenger RNAs (mRNAs), and TGF-beta 1 proteins in the different hepatic lesions suggests that TGF-beta isoforms may play a role in the pathogenesis of quartz-induced fibrosis, cirrhosis, liver cell adenoma, and carcinoma.
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PMID:Hepatic silicosis, cirrhosis, and liver tumors in mice and hamsters: studies of transforming growth factor beta expression. 862 Nov 63

To elucidate the relevance of transforming growth factor (TGF)-beta 1 and platelet-derived growth factor (PDGF)-B to the pathogenesis of pulmonary fibrosis, we introduced each of these expression vectors via trachea into Wistar rat to overexpress them locally in the lungs by hemagglutinating virus of Japan (HVJ)-liposome method. The TGF-beta 1 gene induced significant proliferatin of fibroblasts and deposition of collagen fibrils with mild cellular infiltration. The PDGF-B gene induced mild fibrotic changes with some cellular infiltration. These findings suggest that both factors may be very closely relevant to the pathogenesis of lung fibrosis.
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PMID:[Role of TGF-beta and PDGF on the pathogenesis of pulmonary fibrosis--analysis by in vivo gene transfer]. 883 90

Transforming growth factor (TGF)-beta 1 may potentiate wound healing and fibrosis by stimulating fibroblast collagen deposition. TGF-beta 1 is implicated in the pathogenesis of pulmonary fibrosis, but the role of TGF-beta 2 and TGF-beta 3 remains unclear. We examined their effects on lung fibroblast procollagen metabolism in vitro and localized their gene expression during bleomycin-induced lung fibrosis using in situ hybridization with digoxigenin-labeled riboprobes. All three isoforms stimulated fibroblast procollagen production. TGF-beta 3 was the most potent and also reduced procollagen degradation. In normal mouse lung, TGF-beta 1 and TGF-beta 3 mRNA transcripts were abundant in bronchiolar epithelium. After bleomycin, TGF-beta 1 gene expression was maximally enhanced at 10 days, with the signal being predominant in macrophages. Signal was also enhanced in mesenchymal, pulmonary endothelial, and mesothelial cells. After 35 days, the pattern of TGF-beta 1 gene expression returned to that of control lung. TGF-beta 3 gene expression remained unchanged throughout compared with controls. TGF-beta 2 mRNA was not detected with the antisense probe, but signal obtained with the sense probe suggests the presence of a naturally occurring antisense. This study demonstrates that TGF-beta 1, -beta 2, and -beta 3 all exert profibrotic effects in vitro. However, TGF-beta isoform gene expression is differentially controlled during experimental pulmonary fibrosis with TGF-beta 1 the predominant isoform expressed during pathogenesis.
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PMID:Transforming growth factors-beta 1, -beta 2, and -beta 3 stimulate fibroblast procollagen production in vitro but are differentially expressed during bleomycin-induced lung fibrosis. 906 Aug 36

Integrin activation promotes the survival of endothelial cells undergoing diverse forms of stress. Here we determined the ability of integrins to inhibit DNA strand breakage by bleomycin (BLM), a DNA-cleaving antitumor antibiotic that causes acute endothelial injury and subsequent pulmonary fibrosis. We found that BLM produced DNA breakage in cultured murine lung endothelial cells (MLEC) within 45 min of treatment as measured by DNA sedimentation and in situ labeling of 3'-OH by nick translation (ISNT). Two hours after the removal of BLM, we found a marked but incomplete reduction in DNA strand breakage as measured by ISNT, indicating that the damage was reversible. DNA sedimentation and ISNT demonstrated that strand breakage due to BLM was inhibited in MLEC cultured on fibronectin, and no evidence of breakage was found 2 h after removal of the drug in ISNT experiments. Gelatin, type IV collagen, laminin, and the integrin ligand peptide Gly-Arg-Gly-Asp-Ser-Pro, but not the inactive Gly-Arg-Ala-Asp-Ser-Pro peptide, also inhibited DNA strand breakage. Activation of integrins, either by coating surfaces with antibodies to alpha 5-, beta 1-, or beta 3-integrin subunits or by receptor clustering with the soluble antibodies, inhibited BLM-induced DNA breakage. Inhibition of BLM-induced DNA strand breakage by soluble beta 1-integrin antibody increased with increasing antibody concentration and duration of receptor clustering before BLM treatment. Thus integrin activation protects pulmonary endothelial cells from the genotoxic effects of BLM.
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PMID:Integrin activation protects pulmonary endothelial cells from the genotoxic effects of bleomycin. 931 96

Bleomycin (BLM) induction of lung fibrosis in mice is an established model to study the mechanism of pulmonary fibrosis. Cytokine secretion has been implicated as a fundamental component of the lung fibrotic process observed in response to BLM. Among the cytokines implicated in lung fibrosis, Tumor necrosis factor (TNF) alpha has been considered to play a fundamental role. In the present study, we characterized the cellular sources of TNF during BLM-induced lung injury and examined the importance of TNF receptors in this process. To characterize the expression of TNF, we utilized two strains of mice, one sensitive (C57BL/6) and one resistant (BALB/c) to BLM-induced lung injury. Mice received BLM (120 mg/kg total) or saline, as control, by multiple subcutaneous injections. BLM induced the development of inflammation in subpleural areas only in the lungs of BLM-sensitive mice. These subpleural areas were characterized by infiltration of CD68-positive macrophages and increased collagen deposition. BLM enhanced the expression of TNF mRNA in BLM-sensitive, but not in BLM-resistant, mice. In situ hybridization studies localized the expression of TNF in the areas of BLM-induced inflammation in 6% and 27% of macrophages at 14 and 21 days post BLM treatment. In addition to TNF, BLM exposure resulted in the upregulated expression of transforming growth factor (TGF)-beta 1, but not interleukin (IL)-1, mRNA in the lungs of both murine strains at 14 and 21 days. This upregulated expression of TGF-beta 1 mRNA was greater in the lungs of BLM-sensitive mice. In separate experiments, double TNF receptor knockout mice were exposed to BLM. These animals demonstrated an increased expression of TNF, but not TGF-beta 1, mRNA in response to BLM and did not exhibit histologic evidence of lung injury following BLM exposure. In summary, the upregulation of TNF mRNA in macrophages correlated with the appearance of inflammation following BLM exposure and was limited to the BLM-sensitive strain. Furthermore, in addition to the release of the TNF ligand, it appears that the presence of TNF receptors is necessary for the development of BLM-induced lung injury, and signaling through these receptors may contribute to the regulation of the TGF-beta 1 mRNA expression observed in response to bleomycin. These results provide further support for a role of macrophages and TNF in the induction of lung inflammation.
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PMID:Expression of TNF and the necessity of TNF receptors in bleomycin-induced lung injury in mice. 983 61

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