Versican A-subdomain is required for its adequate function in dermal development.

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  • Additional Information
    • Source:
      Publisher: Informa Healthcare Country of Publication: England NLM ID: 0365263 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1607-8438 (Electronic) Linking ISSN: 03008207 NLM ISO Abbreviation: Connect Tissue Res Subsets: MEDLINE
    • Publication Information:
      Publication: London : Informa Healthcare
      Original Publication: New York, Gordon and Breach Science Publishers.
    • Subject Terms:
    • Abstract:
      Versican, a large chondroitin sulfate (CS) proteoglycan, serves as a structural macromolecule of the extracellular matrix (ECM) and regulates cell behavior. We determined the function of versican in dermal development using Vcan Δ3/Δ3 mutant mice expressing versican with deleted A-subdomain of the N-terminal G1 domain. The mutant versican showed a decreased hyaluronan (HA)-binding ability and failed to accumulate in the ECM. In the early developmental stage, Vcan Δ3/Δ3 dermis showed a decrease in versican expression as compared with WT. As development proceeded, versican expression further decreased to a barely detectable level, and Vcan Δ3/Δ3 mice died at the neonatal period (P0). At P0, Vcan Δ3/Δ3 dermis exhibited an impaired ECM structure and decreased cell density. While the level of collagen deposition was similar in both genotypes, collagen biosynthesis significantly decreased in Vcan Δ3/Δ3 fibroblasts as compared with that in wild type (WT). Transforming growth factor β (TGFβ) signaling mediated through the Smad2/3-dependent pathway was down-regulated in Vcan Δ3/Δ3 fibroblasts and a reduced TGFβ storage in the ECM was observed. Microarray analysis revealed a decrease in the expression levels of transcription factors, early growth response (Egr) 2 and 4, which act downstream of TGFβ signaling. Thus, our results suggest that A-subdomain is necessary for adequate versican expression in dermis and that versican is involved in the formation of the ECM and regulation of TGFβ signaling.
    • Contributed Indexing:
      Keywords: Collagen; TGFβ; extracellular matrix; hyaluronan; versican
    • Accession Number:
      0 (Vcan protein, mouse)
      126968-45-4 (Versicans)
    • Publication Date:
      Date Created: 20170511 Date Completed: 20190404 Latest Revision: 20191210
    • Publication Date:
      20250114
    • Accession Number:
      10.1080/03008207.2017.1324432
    • Accession Number:
      28488903