Tissue
fibrosis accounts for considerable chronic morbidity in certain
connective tissue diseases. Knowledge of the pathobiology of this complication, particularly the identification of fibrogenic
proteins, is now sufficiently advanced to consider novel therapeutic strategies to interfere with pathological fibrogenesis. Studies in a murine model of the helminthic
infection,
schistosomiasis mansoni, led to the discovery of a novel fibrogenic
protein,
fibrosin. Molecular analysis suggests that the domain of cloned
fibrosin cDNA that encodes the fibrogenically active moiety of the
protein is highly conserved in mice and humans, but lacks significant sequence homology with other known cDNAs. Native
fibrosin, as well as a synthetic
fibrosin peptide, stimulate a variety of relevant responses in fibroblasts. Several cell types can produce
fibrosin, including CD4+ lymphocytes and fibroblasts themselves. Observations in experimental
schistosomiasis and in scleroderma reveal two possible mechanisms by which
fibrosin might be involved in
fibrosis. These observations could have implications for diagnosis and novel therapeutic strategies for
fibrosis that complicates
connective tissue diseases.