TY - JOUR
T1 - Gene expression of transforming growth factor β1 and extracellular matrix proteins in murine Schistosoma mansoni infection
AU - Kresina, Thomas F.
AU - He, Qing
AU - Esposti, Silvia Degli
AU - Zern, Mark A
PY - 1994
Y1 - 1994
N2 - 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.
AB - 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.
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U2 - 10.1016/0016-5085(94)90126-0
DO - 10.1016/0016-5085(94)90126-0
M3 - Article
C2 - 8076764
AN - SCOPUS:0028070687
VL - 107
SP - 773
EP - 780
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 3
ER -