Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These experiments were conducted to study the possible involvement of macrophage-derived gelatinases in the bleomycin-induced model of pulmonary fibrosis. Normal rat alveolar macrophages and the rat alveolar macrophage cell line NR8383 were stimulated in vitro with 0-1.0 microgram/ml bleomycin for 18 h. Gelatinase activity in the medium was assayed on zymograms in which gelatin or collagen were used as substrates. Macrophages stimulated with 0.01-1.0 microgram/ml of bleomycin secreted significantly more of a 92-kDa gelatinase than did unstimulated controls. Addition of cycloheximide during stimulation decreased gelatinase activity by 86 +/- 4%, and activity was completely inhibited by the addition of EDTA to zymograms. This gelatinase degraded denatured type I collagen and native type IV collagen. Western blot analysis using a monoclonal mouse anti-rat antibody demonstrated that this enzyme was the same as a metalloproteinase secreted by rat mammary carcinoma cells. Gelatinase secreted by macrophages in fibrotic lungs may enhance macrophage migration through the lung and may also be active in the remodeling process.
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PMID:Alveolar macrophage secretion of a 92-kDa gelatinase in response to bleomycin. 750 94

Silicosis is characterized by pulmonary fibrotic changes which consist primarily of an increase in collagen. In this study, anticollagen antibodies in the serum of 134 silicosis patients versus 40 normal subjects were examined and their relationship with immunoglobulin, autoantibodies, and procollagen III peptide (PIIIP) was investigated by enzyme-linked immunosorbent assay (ELISA). The mean levels of anti-human type I collagen (HI) and anti-human type III collagen (HIII) antibodies were significantly higher in the silicosis patients versus the normal subjects (P < 0.001). However, no differences were observed in the mean levels of anti-human type IV collagen (HIV) antibodies in the silicosis patients versus the normal subjects. Anticollagen antibodies in the sera of silicosis patients appear to be formed at an early stage of the disease. We observed a correlation between anticollagen antibodies and immunoglobulin. There was a tendency toward high values of anticollagen antibodies in the sera of patients positive for antinuclear antibodies (ANA) and rheumatoid factor (RF), both of which are autoantibodies. However, no correlation was observed between serum PIIIP and anticollagen antibodies. These observations suggest that, in silicosis, there is a relationship between anticollagen antibodies and immunoglobulins, as well as between anticollagen antibodies and autoantibodies. Measurement of anticollagen antibodies in the sera of silicosis patients offers a useful index for evaluating the prognosis of pulmonary fibrosis and autoimmune abnormality in silicosis.
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PMID:Studies on production of anticollagen antibodies in silicosis. 843 62

The pulmonary arteriole remodeling in Wistar rats with respiratory infection induced by mycoplasma pneumoniae was observed using light microscopy and morphometry. The pulmonary artery pressure (PAP) and index of right ventricular hypertrophy (RVHI) were measured. The intimal and medial hypertrophy can be seen in the pulmonary arterioles, leading to vessel wall thickening and narrowing of the lumina. The total number of the pulmonary arterioles decreased (P < 0.01), and both pulmonary hypertension (Ppa 4.11 +/- 0.19 kPa) and right ventricular hypertrophy (RVHI = 34.96 +/- 3.91%) occurred. In addition, an interstitial pulmonary fibrosis (IPF) was found, in which the content of collagen in the lung tissue changed, i. e., type I collagen increased whereas type III one decreased, and the ratio of type I collagen to type III one increased. It suggested that respiratory infection induced by repeated MP may result in remodeling of pulmonary arterioles and are closely related to pulmonary hypertension.
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PMID:Chronic pulmonary infection caused by Mycoplasma pneumoniae leading to pulmonary arteriole remodeling and pulmonary hypertension in rats. 873 29

Transforming growth factor-beta (TGF-beta) is a cytokine with diverse biological activity. It can regulate the metabolic function of extracellular matrix (ECM) and play an important role in the development of pulmonary fibrosis. Collagen are major ECM components that are responsible for normal lung structure and function. Collagen accumulation is a major feature of pulmonary fibrosis. In order to study the mechanism of pulmonary fibrosis, we examined the effects of TGF-beta on the production, mRNA expression of type I collagen and type IV collagen by cultures of human embryonic lung fibroblasts. The results indicated that TGF-beta can induce collagen formation and type I collagen, type IV collagen mRNA expression without affecting cell proliferation. We concluded that TGF-beta plays a role in collagen accumulation of pulmonary fibrosis and the changes in collagen production appear to be mediated on collagen mRNA level.
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PMID:[The effect of transforming growth factor-beta on collagen expression by human embryonic fibroblasts]. 876 81

Pulmonary eosinophilic granuloma is characterized by infiltration of the lungs with fibronodular lesions containing specialized Langerhans' cells. In some patients, progressive pulmonary fibrosis leads to significant respiratory impairment. Transforming growth factor-beta1 (TGF-beta1) promotes fibrosis by enhancing the synthesis of extracellular matrix components. The role of TGF-beta1 in promoting fibrosis in the setting of pulmonary eosinophilic granuloma is currently unknown. We used immunohistochemistry to evaluate the extent and distribution of TGF-beta1 and the extracellular matrix components type I collagen and decorin, a TGF-beta1-binding proteoglycan. Lung biopsies from 11 patients with pulmonary eosinophilic granuloma were evaluated. In biopsies with active inflammatory lesions containing Langerhans' cells, hyperplastic type 2 pneumocytes and alveolar macrophages within and surrounding the fibronodular lesions contained abundant TGF-beta1. Langerhans' cells were consistently devoid of immunoreactive TGF-beta1. Active inflammatory lesions also exhibited staining for decorin, in a loosely organized distribution. Advanced fibrotic lesions of eosinophilic granuloma, containing minimal inflammatory cells and few or no Langerhans' cells, exhibited weak or absent staining for TGF-beta1 within either hyperplastic type 2 pneumocytes or alveolar macrophages. The fibroconnective tissues of these advanced fibrotic lesions consistently revealed dense staining for decorin. Through their actions on extracellular matrix protein accumulation, TGF-beta1 and the TGF-beta1-binding proteoglycan decorin may modulate fibrotic repair accompanying pulmonary eosinophilic granuloma.
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PMID:Tissue localization of transforming growth factor-beta1 in pulmonary eosinophilic granuloma. 891 75

We studied the kinetic alterations of angiotensin-II (A-II) and nitric oxide (NO) in radiation pulmonary fibrosis (RPF) to determine the roles of these two types of vasoactive substances in the pathogenesis of RPF. We irradiated the right hemithorax of male Wistar rats with single doses of 0, 15, and 30 Gy of 60Co gamma rays and we examined the lung parenchyma at 1, 3, 5, and 7 months following the radiation. The rats were killed at the stated intervals and samples were obtained from the right lung. We measured types I and III procollagen mRNA by in situ hybridization and demonstrated the synthesis and distribution of A-II in the pulmonary tissue by immunohistochemistry. The formation and kinetic alterations of types I and III collagen were analyzed under polarized light microscope using Sirius Red stain. The hydroxyproline (Hyp) content was measured in the pulmonary tissue after digestion with HCl. A-II radiation immunoactivity (RIA) was assayed in pulmonary tissue homogenate. Pulmonary NO content, NO synthase (NOS), and the angiotensin converting enzyme (ACE) activities were also measured. Our results showed that types I and III collagen genes began to be expressed 1 month after irradiation. Type I collagen gene increased significantly, reaching its peak 3 months after irradiation. As the irradiation dosage was increased from 15 to 30 Gy, the type I collagen gene content increased significantly, while type III significantly decreased. The Hyp content increased with the passage of time after irradiation. Pulmonary A-II RIA increased significantly with the dose of irradiation and was chiefly produced by fibroblasts and macrophages in the interstitium, bronchiolar epithelium, and the anteriolar wall. Pulmonary NO and NOS activities decreased following irradiation. One month following irradiation, the expression of the type I collagen gene begins to increase, with a significant increase in both Hyp and type I collagen 3 months after irradiation. The histogenesis of RPF may be related to A-II. The interstitial cells, the bronchiolar epithelium, and the arteriolar wall can produce A-II and need not pass through the ACE pathway. Our results suggest that the A-II increase and NO decrease may have a role in the pathogenesis of RPF.
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PMID:Kinetic alterations of angiotensin-II and nitric oxide in radiation pulmonary fibrosis. 954 51

Taurine has the ability to resist the action of oxygen-free radicals by protecting cytomembranes. L-arginine increases the nitric oxide in the organism, inhibiting some types of abnormal cell proliferation. We examined the actions and protective mechanisms of these two substances against radiation pulmonary fibrosis. The mRNA transcription and the distribution of pulmonary types I and III procollagen were measured by in situ hybridization. Type I and type III collagen in the interalveolar septa and the change ratio between the two types were assayed using Sirius Red staining and polarizing microscopy. Angiotensin converting enzyme (ACE), hydroxyproline (Hyp), malondialdehyde (MDA), and nitric oxide (NO) were measured in lung tissue after irradiation. We found that, following administration of taurine or arginine, the mRNA transcription of procollagen types I and III significantly decreased in the pulmonary tissue 3 months after irradiation and the Hyp content was lower, especially after the administration of arginine. The extent of the radiation-induced decrease in ACE activity was markedly attenuated. As a substrate of NO production, arginine can significantly increase the pulmonary NO content. We conclude that the administration of taurine or arginine can significantly decrease the mRNA transcription of procollagen and the synthesis of type I collagen in the interalveolar septa and can decrease the Hyp content of the pulmonary tissue. Following irradiation, NO can attenuate the radiation-induced decrease in ACE activity. Our study suggests that exogenous NO and taurine significantly protect against radiation pulmonary injury.
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PMID:The protective action of taurine and L-arginine in radiation pulmonary fibrosis. 954 52

Deposition of types I and III collagen is a typical feature in the development of pulmonary fibrosis. We assessed the propeptides of these procollagens as prognostic markers in 18 patients with fibrosing alveolitis. We analyzed the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal propeptide of type I procollagen (PICP) from samples of bronchoalveolar lavage fluid (BALF) and serum, and also estimated their concentrations in epithelial lining fluid (ELF) by the urea method. The level of PIIINP in serum (p < 0.05), BALF (p < 0.05), and ELF (p < 0.05), and the levels of PICP in BALF (p < 0.001) and ELF (p < 0.001) but not in serum, were significantly increased in the patients with fibrosing alveolitis as compared with 17 controls who had been investigated for minor respiratory symptoms. In the BALF and ELF of patients with fibrosing alveolitis, PICP but not PIIINP had significant negative correlations with the specific diffusion coefficient for carbon monoxide (DLCO/ VA). The amino-terminal propeptide of type III procollagen and the carboxy-terminal propeptide of type I procollagen in BALF correlated significantly with one another. During the follow-up period of 6 yr, seven of the 18 patients with fibrosing alveolitis died of the disease, 3 others died of malignancy, and one patient died from an unknown cause. DLCO (p < 0.05) differed significantly between the surviving patients and those who died of fibrosing alveolitis, and detectable PIIINP in BALF predicted death from fibrosing alveolitis (p = 0.05). In conclusion, these results show that PIIINP in BALF, ELF, and serum, and PICP in BALF and ELF, are increased in patients with fibrosing alveolitis. A high level of PICP in BALF, and especially in ELF, suggests a chronic process and increased synthesis of type I collagen in the lungs, whereas PIIINP in BALF and ELF suggests active disease and a poor prognosis.
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PMID:Type III and type I procollagen markers in fibrosing alveolitis. 1005 Dec 56

Secreted protein acidic and rich in cysteine (SPARC) has been shown to be coexpressed with type I collagen in tissues undergoing remodeling and wound repair. We speculated that SPARC is required for the accumulation of collagen in lung injury and that its absence would attenuate collagen accumulation. Accordingly, we have assessed levels of collagen in SPARC-null mice in an intratracheal bleomycin-injury model of pulmonary fibrosis. Eight- to ten-week-old SPARC-null and wild-type (WT) mice received bleomycin (0.0035 U/g) or saline intratracheally and were subsequently killed after 14 days. Relative levels of SPARC mRNA were increased 2.7-fold (P < 0.001) in bleomycin-treated WT lungs in comparison with saline-treated lungs. Protein from bleomycin-treated WT lung contained significantly more hydroxyproline (191.9 microg/lung) than protein from either bleomycin-treated SPARC-null lungs or saline-treated WT and SPARC-null lungs (147.4 microg/lung, 125.4 microg/lung, and 113. 0 microg/lung, respectively; P < 0.03). These results indicate that SPARC is increased in response to lung injury and that accumulation of collagen, as indicated by hydroxyproline content, is attenuated in the absence of SPARC. The properties of SPARC as a matricellular protein associated with cell proliferation and matrix turnover are consistent with its participation in the development of pulmonary fibrosis.
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PMID:Collagen accumulation is decreased in SPARC-null mice with bleomycin-induced pulmonary fibrosis. 1048 71

Pulmonary fibrosis is a well-recognized feature of acute respiratory distress syndrome (ARDS). Using immunoassays of bronchoalveolar lavage (BAL), fluid we investigated the synthesis of type I procollagen (PICP) and type I/II collagen degradation products (COL2-3/4C(short) neoepitope) in patients with ARDS, acute lung injury (ALI), subjects with risk factors for ARDS (At Risk), and healthy/ventilated control subjects. PICP was measured by ELISA as a marker of type I procollagen synthesis. COL2-3/4C(short) neoepitope was measured by an inhibition ELISA as a marker of collagenase degradation of type I/II collagen. BAL was performed initially within 48 h of ventilation (Day 1) and then subsequently on Day 4. Dilution of epithelial lining fluid (ELF) was corrected for by plasma urea comparison. Increased PICP levels were observed in the ELF from ARDS and ALI subjects on Day 1 compared with subjects At Risk (median values, 124.9 and 95.0 ng/ml versus 38.0 ng/ml, respectively, p < 0.0005). By contrast, the levels of COL2-3/4C(short) neoepitope were significantly reduced in the subjects with ARDS versus the At Risk subjects (13.22 ng/ml versus 32.33 ng/ml, p < 0.0005). This translated into a greatly increased PICP:COL2-3/4C(short) ratio in the subjects with ARDS (p < 0.0001). There was a significant decline in the PICP level in the subjects with ARDS between Days 1 and 4 (n = 15, p < 0.05). Linear regression analysis showed a significant association between PICP and lung injury score in the subjects with ARDS (p = 0.01). Our data suggests an early shift in balance between type I collagen synthesis and degradation by collagenase. The resultant increase in type I collagen would favor matrix deposition and the development of pulmonary fibrosis in the lungs of subjects with ARDS.
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PMID:Changes in collagen turnover in early acute respiratory distress syndrome. 1058 5


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