title: Mice lacking cystathionine beta synthase have lung fibrosis and air space enlargement.
abstract: 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.
authors.affiliation: EA 3508, Université Paris Diderot, Paris 7, Case 7104, 2 Place Jussieu, 75251 Paris cedex 05, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Hamelet
authors.forename: Nicole
authors.initials: N
authors.lastname: Maurin
authors.forename: Romain
authors.initials: R
authors.lastname: Fulchiron
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Delabar
authors.forename: Nathalie
authors.initials: N
authors.lastname: Janel
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003541:Cystathionine beta-Synthase / Q000172:deficiency*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000473:pathology; D006710:Homocysteine / Q000097:blood; D020138:Hyperhomocysteinemia / Q000150:complications; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology; D011658:Pulmonary Fibrosis / Q000201:enzymology / Q000473:pathology*
chemical_list: D006710:Homocysteine; D003541:Cystathionine beta-Synthase