Fibrosin, a novel fibrogenic protein: discovery, cloning and implications for fibrotic disorders.
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.
Wyler
D J
DJ
New England Medical Center and Tufts University School of Medicine, Boston, Mass. 02111, USA.
D000818:Animals; D003001:Cloning, Molecular; D003240:Connective Tissue Diseases / Q000150:complications; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis / Q000209:etiology; D006099:Granuloma / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000473:pathology; D008222:Lymphokines / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use; D051379:Mice; D012555:Schistosomiasis mansoni / Q000378:metabolism
D008222:Lymphokines; C092591:fibrosin