Transient expression of lysyl oxidase by liver myofibroblasts in murine schistosomiasis.

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Sommer, P. | Gleyzal, C. | Raccurt, M. | Delbourg, M. | Serrar, M. | Joazeiro, P. | Peyrol, S. | Kagan, H. | Trackman, Pc | Grimaud, Ja

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International audience. BACKGROUND: Murine schistosomiasis provides an experimental model of reversible fibrosis. The lysyl oxidase catalyzes the first step of collagen and elastin enzymatic cross-linking and appears to be a crucial factor in stabilizing the neosynthesized extracellular matrix in the liver. EXPERIMENTAL DESIGN: A cDNA probe encoding a portion of the murine lysyl oxidase was cloned, and antibodies were raised against the corresponding recombinant peptide expressed as a fusion protein. Both tools were used to examine the expression of the lysyl oxidase mRNAs and peptides, all within granulomas and cells extracted from infected liver. RESULTS: Transient up-regulation of two dominant 4.5 kb and 5.5 kb transcripts was observed among four mRNAs hybridizing with the lysyl oxidase cDNA probe during the development of granulomas. An identical time course was obtained for alpha 1(I) procollagen messenger expression. The lysyl oxidase expression was observed in type I collagen producing cells mainly localized at the periphery of fibroinflammatory granulomas and it disappeared in late granulomas. The lysyl oxidase and type I collagen expressing cells, located within granulomas, exhibited the characteristics of myofibroblasts, as judged by their expression of alpha-smooth muscle actin and desmin and by their ultrastructural morphology. Four antigenically related peptides were immunopurified from an enriched preparation of myofibroblast-like cells extracted from infected mouse liver. Two of these peptides had the molecular weight of prolysyl oxidase (50,000) and activated lysyl oxidase (32,000). The two others (28,000 and 66,000) might correspond to cleavage product or dimeric form respectively. CONCLUSIONS: This study demonstrates that the lysyl oxidase was transiently up-regulated at the transcriptional level parallely to alpha(1)I procollagen within developing granulomas. Myofibroblasts are involved in the expression of the lysyl oxidase which may be secreted as a proenzyme and an activated enzyme.BACKGROUND: Murine schistosomiasis provides an experimental model of reversible fibrosis. The lysyl oxidase catalyzes the first step of collagen and elastin enzymatic cross-linking and appears to be a crucial factor in stabilizing the neosynthesized extracellular matrix in the liver. EXPERIMENTAL DESIGN: A cDNA probe encoding a portion of the murine lysyl oxidase was cloned, and antibodies were raised against the corresponding recombinant peptide expressed as a fusion protein. Both tools were used to examine the expression of the lysyl oxidase mRNAs and peptides, all within granulomas and cells extracted from infected liver. RESULTS: Transient up-regulation of two dominant 4.5 kb and 5.5 kb transcripts was observed among four mRNAs hybridizing with the lysyl oxidase cDNA probe during the development of granulomas. An identical time course was obtained for alpha 1(I) procollagen messenger expression. The lysyl oxidase expression was observed in type I collagen producing cells mainly localized at the periphery of fibroinflammatory granulomas and it disappeared in late granulomas. The lysyl oxidase and type I collagen expressing cells, located within granulomas, exhibited the characteristics of myofibroblasts, as judged by their expression of alpha-smooth muscle actin and desmin and by their ultrastructural morphology. Four antigenically related peptides were immunopurified from an enriched preparation of myofibroblast-like cells extracted from infected mouse liver. Two of these peptides had the molecular weight of prolysyl oxidase (50,000) and activated lysyl oxidase (32,000). The two others (28,000 and 66,000) might correspond to cleavage product or dimeric form respectively. CONCLUSIONS: This study demonstrates that the lysyl oxidase was transiently up-regulated at the transcriptional level parallely to alpha(1)I procollagen within developing granulomas. Myofibroblasts are involved in the expression of the lysyl oxidase which may be secreted as a proenzyme and an activated enzyme.

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