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)

To investigate the biological effectiveness of proton beams in the development of pulmonary fibrosis the lungs of male 7-week-old Wistar rats were locally irradiated with a single dose of 10-50 Gy of 250 kV X-rays and modulated, 250 MeV protons at Particle Radiation Medical Science Center (PARMS). Animals were sacrificed serially after 3, 6, 9 and 12 months at which times the development of the fibrotic lesion in alveolar walls and peribronchial connective tissues was assessed quantitatively by analysis of microscopic images of Azan-Mallory stained sections. Fibrosis index (FI) values in alveolar walls and peribronchial tissues were defined as the fraction (in percent) of a specific image area, the gray level of which represents collagen deposits. Using this FI values, the increase of fibrotic lesion following 0-40 Gy of X-rays irradiation as a function of time were observed better in alveolar walls than in peribronchial tissues. Compared with 250 kV X-rays, 30 Gy of proton beams irradiation produced less increase in the time course of FI values of alveolar walls and dose-response curve at 12 months later suggested that the fibrotic lesion in alveolar walls after protons exposure of the doses above 30 Gy might develop more slowly.
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PMID:[Late radiation fibrosis in rat lung following protons and 250 kV X-rays irradiation]. 216 62

It is well known that the intake of paraquat (PQ), an herbicide, causes severe lung injury at chronic phases. We examined the intrapulmonary gene expression of cytokines and growth factors after PQ administration. To induce lung injury, C57BL/6 mice were intraperitoneally injected twice a week with 20 mg/kg of PQ. Histopathologically, at the early phase, lots of alveolar spaces contained edematous fluid. At 3 weeks after PQ challenge, a marked thickening of the alveolar walls with the accumulation of macrophages and T cells was found. Azan staining revealed the patchy distribution of collagen accumulation, indicating pulmonary fibrosis. Consistently, intrapulmonary hydroxyproline contents were significantly elevated, compared with the controls. Semi-quantitative RT-PCR analysis demonstrated that the gene expression of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 were significantly increased at 3 weeks after PQ challenge compared with the controls. The mRNA expression of macrophage inflammatory protein (MIP)-1alpha and MIP-2 was significantly enhanced at 1 and 2 weeks after PQ treatment, respectively. Moreover, PQ-treated mice showed enhanced gene expression of fibrogenic growth factors such as transforming growth factor-beta, platelet-derived growth factor-A, acidic fibroblast growth factor, and hepatoctyte growth factor at 2 and/or 3 weeks after PQ challenge. The synergistic effects of these molecules are presumed to cause pulmonary fibrosis due to PQ challenge.
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PMID:Gene expression of cytokines and growth factors in the lungs after paraquat administration in mice. 1632 72

Methotrexate (MTX) has been used as the first-line disease-modifying antirheumatic drug (DMARD) in patients with early progressive rheumatoid arthritis (RA). Several severe side effects such as myelosuppression, hepato-, nephro-, and pulmonary toxicities have been reported. However, the pathogenic mechanism of MTX-induced pulmonary fibrosis is still unknown. Here, we evaluated the morphological and biological changes of the pulmonary fibrosis in mice treated with MTX. Three, four and five weeks after consecutive administration of MTX (3 mg/kg/day), hydroxyproline content in the lung tissues increased significantly to about 2 times higher that of the control level. This result closely reflected to the results of hematoxylin and eosin (HE) and Azan stains. Immunohistochemical analysis revealed that MTX treatment resulted in a decrease of alveolar epithelial cells and an increase of fibroblast cells in the mouse lung tissues. When we examined the effects of MTX on primary mouse alveolar epithelial cell (MAEC) and mouse lung fibroblast (MLF) survival in vitro, the efficiency of MTX-induced cytotoxicity and apoptosis in MAEC was more sensitive than MLF cells. Thus, our results indicate that the administration of MTX by an oral route could induce a fibrotic response with cell dysfunction of the alveolar epithelium by which MTX-induced apoptosis. Our results thus suggest that MTX could induce alveolar epithelial cell injury and resulted in the loss of integrity of the alveolar-capillary barrier basement membranes followed by the recruitment and proliferation of myofibroblasts with the deposition of collagens.
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PMID:Induction of pulmonary fibrosis by methotrexate treatment in mice lung in vivo and in vitro. 2093 Apr 60