GENE-EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 AND EXTRACELLULAR-MATRIX PROTEINS IN MURINE SCHISTOSOMA-MANSONI INFECTION

Background/Aims: The study of Schistosoma-induced hepatic fibrosis in murine Schistosoma mansoni infection has elucidated the nature of hepatic fibrosis in humans. In the present study, fibrogenic gene expression was determined in murine S. mansoni infection during primary infection, after chemotherapy with praziquantel, and during secondary infection. Methods: Both histomorphometeric analysis and Northern blot profiles were performed. Results: Histomorphometric analysis of granulomatous inflammation showed smaller hepatic fibrotic granulomata after chemotherapy and during secondary infection. Albumin gene expression remained relatively constant throughout primary infection, chemotherapy, and secondary infection. Fibronectin gene expression in primary infection was comparable with the level observed in noninfected mice and was reduced by chemotherapy. Reinfection resulted in augmented expression levels equal to primary infection levels. Osteonectin gene expression was active in primary infection, was reduced by chemotherapy, and was actively reexpressed in secondary infection. Interstitial matrix macromolecules, types I and III collagen, and basement membrane collagen showed high levels of gene expression in primary infection, were virtually terminated by chemotherapy, and were reexpressed on reinfection. The gene expression of transforming growth factor β1, a major, fibrogenic cytokine, paralleled collagen expression. Conclusions: Chemotherapy of schistosomiasis initiated a dramatic decrease in steady-state messenger RNA levels of major proteins associated with fibrosis; reinfection resulted in a reexpression of these genes. © 1994.