title: Lung fibroblast clones from normal and fibrotic subjects differ in hyaluronan and decorin production and rate of proliferation.
abstract: Development of fibrosis involves an increase in the deposition of connective tissue components including collagens, fibronectin and proteoglycans. One hypothesis to account for matrix deposition in fibrosis is that fibroblast with differing matrix producing capacity are involved in the fibrotic process. To test this hypothesis, primary fibroblast cultures and clones derived from these primary lines were established from the lung tissue of control patients and patients with pulmonary fibrosis. The primary lines and derived clones were studied in relation to their capacity to proliferate and to produce proteoglycans and hyaluronan. Primary fibroblast cultures and clones from normal subjects and patients with lung fibrosis differed considerably, with up to 13-fold difference, in both hyaluronan and proteoglycan production. The major proteoglycan produced was decorin in both controls and cultures from fibrotic patients, while cultures from patients with lung fibrosis had a higher expression of mRNA for both collagen and decorin. Clones derived from a primary line from a fibrotic patient secreted 3-fold greater amounts of decorin than those from a control subject. Furthermore, a negative correlation between proliferation and synthesis of decorin was noted. We suggest that different fibroblast clones accumulate in the lung, and that specific cell populations of high decorin producing fibroblasts may exist which are crucial in the pathogenesis of fibrosis.
authors.affiliation: Department of Cell and Molecular Biology, C13, BMC, Lund University, S-221 84 Lund, Sweden. gunillawestergren-thorsson@medkem.lu.se
authors.forename: Gunilla
authors.initials: G
authors.lastname: Westergren-Thorsson
authors.forename: Patricia
authors.initials: P
authors.lastname: Sime
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
authors.forename: Jack
authors.initials: J
authors.lastname: Gauldie
authors.forename: Bengt
authors.initials: B
authors.lastname: Särnstrand
authors.forename: Anders
authors.initials: A
authors.lastname: Malmström
mesh_terms: D049109:Cell Proliferation; D002999:Clone Cells; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000166:cytology / Q000473:pathology*; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis* / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000473:pathology; D011509:Proteoglycans / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology*
chemical_list: C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D006820:Hyaluronic Acid