title: The elongated first fibronectin type III domain of collagen XIV is an inducer of quiescence and differentiation in fibroblasts and preadipocytes.
abstract: Collagen XIV (CXIV) is a fibril-associated collagen that is mainly expressed in well differentiated tissues and in late embryonic development. Because CXIV is almost absent in proliferating and/or dedifferentiated tissues, a functional role in maintaining cell differentiation is suspected. We demonstrate antiproliferative, quiescence- and differentiation-inducing effects of human CXIV and its recombinant fragments on mesenchymal cells. In primary human fibroblasts, in mouse 3T3 fibroblasts and in 3T3-L1 preadipocytes, CXIV reduced de novo DNA synthesis by 75%, whereas cell numbers and viability remained unaltered. Cells showed no signs of apoptosis, and maximal proliferation was restored when serum was supplemented, thus indicating that CXIV induced reversible cellular quiescence. Exposure of fibroblasts to CXIV in vitro led to cellular bundles and clusters. CXIV also triggered trans-differentiation of 3T3-L1 preadipocytes into adipocytes, as could be shown by lipid accumulation and by expression of the glucose transporter Glut4. These effects were also observed with the amino-terminal recombinant fragment Gln(29)-Pro(154) that harbors the first fibronectin type III domain and a 39-amino-acid extension, whereas no activity was found for all other recombinant CXIV fragments. Based on these finding the development of small molecular analogs that modulate fibroblast cell growth and differentiation, e.g. in wound healing and fibrosis, seems feasible.
authors.affiliation: Department of Gastroenterology, Charité Campus, Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Ruehl
authors.forename: Ulrike
authors.initials: U
authors.lastname: Erben
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.forename: Christine
authors.initials: C
authors.lastname: Wagner
authors.forename: Anita
authors.initials: A
authors.lastname: Zeller
authors.forename: Christian
authors.initials: C
authors.lastname: Freise
authors.forename: Hadi
authors.initials: H
authors.lastname: Al-Hasani
authors.forename: Maik
authors.initials: M
authors.lastname: Loesekann
authors.forename: Michael
authors.initials: M
authors.lastname: Notter
authors.forename: Bianca Maria
authors.initials: BM
authors.lastname: Wittig
authors.forename: Martin
authors.initials: M
authors.lastname: Zeitz
authors.forename: Walburga
authors.initials: W
authors.lastname: Dieterich
authors.forename: Rajan
authors.initials: R
authors.lastname: Somasundaram
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001391:Azo Compounds / Q000494:pharmacology; D001692:Biological Transport; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry*; D005355:Fibrosis / Q000473:pathology; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D005973:Glutamine / Q000737:chemistry; D005982:Glutathione Transferase / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D010920:Placenta / Q000378:metabolism; D011392:Proline / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D013936:Thymidine / Q000737:chemistry; D013997:Time Factors; D014945:Wound Healing
chemical_list: D001391:Azo Compounds; C054447:COL14A1 protein, human; D005353:Fibronectins; D051275:Glucose Transporter Type 4; D006023:Glycoproteins; D008055:Lipids; D011994:Recombinant Proteins; D005973:Glutamine; D003094:Collagen; D011392:Proline; D005982:Glutathione Transferase; C011049:oil red O; D005947:Glucose; D013936:Thymidine