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Neurourol Urodyn ; 23(4): 374-82, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15227657

RESUMO

AIMS: Urinary bladders of patients with myelomeningocele, owing to spina bifida, are often functionally impaired, fibrotic organs. Common to this condition are repeated occurrences of bladder infection and inflammation. Since mast cells have been associated with a fibrogenic response in inflammatory conditions, we investigated the role of mast cell granule product, chymase, as a mediator of myleodysplastic bladder fibrosis. METHODS: Human control and myelodysplastic bladder tissues were stained with Unna's stain and chymase antibody to determine mast cell number and localization. Cell specific localization of collagen mRNAs was determined by in situ hybridization (ISH). In vitro, normal human bladder fibroblasts were treated with recombinant chymase, heparin and inhibitors, and collagen subtype concentration was determined by enzyme linked immunosorbent assay (ELISA). RESULTS: Myelodysplastic bladders were characterized by increased mast cells in the detrusor muscle layer compared to control bladders, as well as mast cell degranulation and increased connective tissue deposition. Both types I and III collagen mRNA localized to fibroblasts surrounding detrusor muscle fascicles, whereas only collagen III mRNA localized to cells within connective tissue infiltrated muscle bundles in myelomeningocele bladder tissue. Chymase treatment of bladder fibroblasts, in vitro, was dose-dependent and resulted in significant increases in both types I and III collagen. Heparin did not alter collagen protein expression, whereas heparin-chymase combination modulated type III collagen expression. Serine protease inhibitor, phenylmethylsulfonlyfluoride, did not inhibit collagen synthesis, whereas denatured chymase resulted in decreased collagenous protein levels. CONCLUSIONS: Bladder fibrosis may be mediated by mast cell chymase stimulation of collagen synthesis.


Assuntos
Mastócitos/enzimologia , Meningomielocele/complicações , Serina Endopeptidases/metabolismo , Bexiga Urinaria Neurogênica/enzimologia , Bexiga Urinaria Neurogênica/patologia , Bexiga Urinária/enzimologia , Adolescente , Degranulação Celular , Células Cultivadas , Criança , Pré-Escolar , Quimases , Colágeno/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Tecido Conjuntivo/metabolismo , Tecido Conjuntivo/patologia , Relação Dose-Resposta a Droga , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Humanos , Hibridização In Situ , Lactente , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/patologia , Fluoreto de Fenilmetilsulfonil/farmacologia , Inibidores de Proteases/farmacologia , RNA Mensageiro/metabolismo , Serina Endopeptidases/administração & dosagem , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/patologia , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinaria Neurogênica/metabolismo
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