Identification and characterization of a fibroblast marker: FSP1.

Abstract

Abstract. We performed subtractive and differential hybridization for transcript comparison between murine fibroblasts and isogenic epithelium, and observed only a few novel intracellular genes which were relatively specific for fibroblasts. One such gene encodes a filament-associated, calcium-binding protein, fibroblast-specific protein 1 (FSP1). The promoter/enhancer region driving this gene is active in fibroblasts but not in epithelium, mesangial cells or embryonic endoderm. During development, FSP1 is first detected by in situ hybridization after day 8.5 as a postgastrulation event, and is associated with cells of mesenchymal origin or of fibroblastic phenotype. Polyclonal antiserum raised to recombinant FSP1 protein stained the cytoplasm of fibroblasts, but not epithelium. Only occasional cells stain with specific anti-FSP1 antibodies in normal parenchymal tissue. However, in kidneys fibrosing from persistent inflammation, many fibroblasts could be identified in interstitial sites of collagen deposition and also in tubular epithelium adjacent to the inflammatory process. This pattern of anti-FSP1 staining during tissue fibrosis suggests, as a hypothesis, that fibroblasts in some cases arise, as needed, from the local conversion of epithelium. Consistent with this notion that FSP1 may be involved in the transition from epithelium to fibroblasts are experiments in which the in vitro overexpression of FSP1 cDNA in tubular epithelium is accompanied by conversion to a mesenchymal phenotype, as characterized by a more stellate and elongated fibroblast-like appearance, a reduction in cytokeratin, and new expression of vimentin. Similarly, tubular epithelium submerged in type I collagen gels exhibited the conversion to a fibroblast phenotype which includes de novo expression of FSP1 and vimentin. Use of the FSP1 marker, therefore, should further facilitate both the in vivo studies of fibrogenesis and the mapping of cell fate among fibroblasts.

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

“…To explore the role of S100A4 + cells in the development of CRC, S100A4-thymidine kinase (TK) transgenic mice were used, 22 , 39 and proliferating S100A4 + cells in these mice could be selectively depleted upon the treatment of ganciclovir (GCV) after the administration of AOM/DSS, as illustrated in Fig. 3A.…”

FSP1+ Fibroblasts Promote Skin Carcinogenesis by Maintaining MCP-1-Mediated Macrophage Infiltration and Chronic Inflammation

“…28 We double-stained the skin tissue with ␣-SMA and FSP1 and found that there were seldom ␣-SMA and FSP1 double positive cells in the TPA-treated skin ( Figure 1B), which is similar with the former discovery in the tumor, 29 indicating that TPA mainly simulated the proliferation of a unique population of FSP1 ϩ fibroblasts that are regarded as the most important class of fibroblasts present in many tissues. 20,30 FSP1 usually serves as a sensitive and specific marker for fibroblasts. 31 Recently, using FSP1 as the promoter in Cre-loxp system, Trimboli et al 32 described that Pten in stromal fibroblasts suppresses mammary epithelial tumors.…”

Localization of HSP47 mRNA in murine bleomycin-induced pulmonary fibrosis

“…However, transitions do occur particularly during oncogenesis [31] and fibrogenesis [32,33]. This process has been particularly studied in renal fibrosis.…”