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PMID:7892239

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Citation

Prakash, S, Robbins, PW and Wyler, DJ (1995) Cloning and analysis of murine cDNA that encodes a fibrogenic lymphokine, fibrosin. Proc. Natl. Acad. Sci. U.S.A. 92:2154-8

Abstract

Tissue fibrosis that complicates chronic inflammation can be a cause of serious morbidity. The molecular links between inflammation and fibrosis appear to be a variety of proteins produced by activated chronic inflammatory cells. Collectively, these fibrogenic cytokines promote the growth of fibroblasts and the production of extracellular matrix that are the characteristic features of fibrotic tissue. In an attempt to clone cDNA for a fibrogenic lymphokine that we had isolated, we transfected COS-7 cells with a cDNA library derived from concanavalin A-stimulated lymphocyte line CDC25. Conditioned medium from the transfected COS-7 cells but not from sham-transfected cells stimulates fibroblast proliferation in vitro. We used heterologous expression in COS-7 cells of pools of CDC25 cDNA and screening for biological activity in conditioned medium to enrich for the cDNA clone(s) that encodes this activity. With this strategy of sib selection we isolated clone 2B3. The culture supernatants of 2B3-transfected COS-7 cells exert maximum growth-stimulating effects on fibroblasts at a dilution of 1:20,000. The isolated cDNA has one open reading frame (216 nucleotides) that has no significant homology with nucleotide sequences that encode other proteins. A synthetic peptide constructed from the deduced amino acid sequence is biologically active in picomolar concentrations, even though it may represent only a portion of the native fibrosin. This lymphokine, which we designate fibrosin, may play a role in regulating fibrogenesis in certain chronic inflammatory diseases.

Links

PubMed PMC42442

Keywords

Amino Acid Sequence; Animals; Antibodies; Base Sequence; CD4-Positive T-Lymphocytes/immunology; Cell Division/drug effects; Cell Line; Cells, Cultured; Cercopithecus aethiops; Cloning, Molecular; Codon; DNA, Complementary/analysis; Fibroblasts/cytology; Fibroblasts/drug effects; Fibrosis; Humans; Infant, Newborn; Kidney; Kinetics; Lymphocyte Activation/drug effects; Lymphokines/biosynthesis; Lymphokines/isolation & purification; Lymphokines/pharmacology; Male; Molecular Sequence Data; Peptides/chemical synthesis; Phosphoprotein Phosphatases/biosynthesis; Phosphoprotein Phosphatases/chemistry; Protein Biosynthesis; Proteins/chemistry; Recombinant Proteins/biosynthesis; Recombinant Proteins/isolation & purification; Recombinant Proteins/pharmacology; Skin/cytology; T-Lymphocytes, Helper-Inducer/immunology; Thymidine/metabolism; Transfection

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:FBRS

enables

GO:0008083: growth factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:FBRS

acts_upstream_of_or_within

GO:0048146: positive regulation of fibroblast proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FBRS

part_of

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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