IDENTIFICATION AND CHARACTERIZATION OF A FIBROBLAST MARKER - FSP1

We performed subtractive and differential hybridization for transcript comparison between murine fibroblasts and isogenic epithelium, and ob served only a few novel intracellular genes which were relatively spec ific for fibroblasts. One such gene encodes a filament-associated, cal cium-binding protein, fibroblast-specific protein 1 (FSP1). The promot er/enhancer region driving this gene is active in fibroblasts but not in epithelium, mesangial cells or embryonic endoderm, During developme nt, FSP1 is first detected by in situ hybridization after day 8.5 as a postgastrulation event, and is associated with cells of mesenchymal o rigin or of fibroblastic phenotype. Polyclonal antiserum raised to rec ombinant FSP1 protein stained the cytoplasm of fibroblasts, but not ep ithelium. Only occasional cells stain with specific anti-FSP1 antibodi es in normal parenchymal tissue. However, in kidneys fibrosing from pe rsistent inflammation, many fibroblasts could be identified in interst itial sites of collagen deposition and also in tubular epithelium adja cent to the inflammatory process. This pattern of anti-FSP1 staining d uring tissue fibrosis suggests, as a hypothesis, that fibroblasts in s ome cases arise, as needed, from the local conversion of epithelium. C onsistent with this notion that FSP1 may be invoked in the transition from epithelium to fibroblasts are experiments in which the in vitro o verexpression of FSP1 cDNA in tubular epithelium is accompanied by con version to a mesenchymal phenotype, as characterized by a more stellat e and elongated fibroblast-like appearance, a reduction in cytokeratin , and new expression of vimentin. Similarly, tubular epithelium submer ged in type I collagen gels exhibited the conversion to a fibroblast p henotype which includes de novo expression of FSP1 and vimentin. Use o f the FSP1 marker, therefore, should further facilitate both the in vi vo studies of fibrogenesis and the mapping of cell fate among fibrobla sts.