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)

Apoptosis is important in developmental biology and in remodeling of tissues during repair. Apoptosis also plays important roles in the progression of many diseases. The cellular and molecular mechanisms of apoptosis, in general, have been extensively demonstrated. However, the causes and the roles of apoptosis of various cell types in the lung are not well understood. We have determined that adenosine/homocysteine causes lung vascular endothelial cell apoptosis by inhibition of carboxyl methylation of the small GTPase, Ras, through inhibition of isoprenylcysteine carboxyl methyltransferase(ICMT) activity, leading to inactivation of Ras and the subsequent disruption of focal adhesion complexes, resulting in cell-extracellular matrix detachment and anoikis. Apoptosis can either ameliorate or exacerbate lung injury, depending upon the cell type. Although apoptosis of polymorphonuclear leukocytes in the lung prevents inflammation and the development of acute respiratory distress syndrome during acute lung injury, Fas/FasL-mediated alveolar epithelial cell apoptosis promotes acute lung injury and pulmonary fibrosis. Lung epithelial and endothelial cell apoptosis also contributes to the development of emphysema. This article focuses on elucidating the mechanisms of adenosine/homocysteine-induced endothelial cell apoptosis. We also review the current understanding of the role of lung cell apoptosis in acute lung injury, pulmonary fibrosis and emphysema.
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PMID:Apoptosis and lung injury. 1645 28

Cystathionine beta synthase (CBS) is a crucial regulator of plasma concentrations of homocysteine. Severe hyperhomocysteinemia due to CBS deficiency confers diverse clinical manifestations, notably pulmonary thrombotic disease. However, the association between hyperhomocysteinemia and chronic obstructive pulmonary disease is not well understood. To investigate the role of hyperhomocysteinemia in lung injury and pulmonary fibrosis, we analyzed the lung of CBS-deficient mice, a murine model of severe hyperhomocysteinemia. The degree of lung injury was assessed by histologic examination. Analysis of profibrogenic factors was performed by real-time quantitative reverse transcription-polymerase chain reaction. CBS-deficient mice develop fibrosis and air space enlargement in the lung, concomitant with an enhanced expression of heme oxygenase-1, pro(alpha)1 collagen type I, transforming growth factor-beta1 and alpha-smooth muscle actin. However, lung fibrosis was found in the absence of increased inflammatory cell infiltrates as determined by histology, without changes in gene expression of proinflammatory cytokines TNFalpha and interleukin 6. The increased expression of alpha-smooth muscle actin and transforming growth factor-beta1 emphasizes the role of myofibroblasts differentiation in case of lung fibrosis due to CBS deficiency in mice.
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PMID:Mice lacking cystathionine beta synthase have lung fibrosis and air space enlargement. 1754 41