Plap-1/asporin positively regulates FGF-2 activity

T. Awata, S. Yamada, K. Tsushima, H. Sakashita, S. Yamaba, T. Kajikawa, M. Yamashita, M. Takedachi, M. Yanagita, M. Kitamura, S. Murakami

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

PLAP-1 is an extracellular matrix protein that is predominantly expressed in the periodontal ligament within periodontal tissue. It was previously revealed that PLAP-1 negatively regulates bone morphogenetic protein 2 and transforming growth factor β activity through direct interactions. However, the interaction between PLAP-1 and other growth factors has not been defined. Here, we revealed that PLAP-1 positively regulates the activity of fibroblast growth factor 2 (FGF-2), a critical growth factor in tissue homeostasis and repair. In this study, we isolated mouse embryonic fibroblasts (MEFs) from Plap-1-/- mice generated in our laboratory. Interestingly, Plap-1-/- MEFs exhibited enhanced responses to bone morphogenetic protein 2 but defective responses to FGF-2, and Plap-1 transfection into Plap-1-/- MEFs rescued these defective responses. In addition, binding assays revealed that PLAP-1 promotes FGF-2-FGF receptor 1 (FGFR1) complex formation by direct binding to FGF-2. Immunocytochemistry analyses revealed colocalization of PLAP-1 and FGF-2 in wild-type MEFs and reduced colocalization of FGF-2 and FGFR1 in Plap-1-/- MEFs compared with wild-type MEFs. Taken together, PLAP-1 positively regulates FGF-2 activity through a direct interaction. Extracellular matrix-growth factor interactions have considerable effects; thus, this approach may be useful in several regenerative medicine applications.

Original languageEnglish
Pages (from-to)1417-1424
Number of pages8
JournalJournal of dental research
Volume94
Issue number10
DOIs
Publication statusPublished - 2015 Oct
Externally publishedYes

Keywords

  • BMP-2
  • Cell differentiation
  • Cell proliferation
  • Extracellular matrix
  • Growth factors
  • Periodontal ligament

ASJC Scopus subject areas

  • Dentistry(all)
  • Medicine(all)

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  • Cite this

    Awata, T., Yamada, S., Tsushima, K., Sakashita, H., Yamaba, S., Kajikawa, T., Yamashita, M., Takedachi, M., Yanagita, M., Kitamura, M., & Murakami, S. (2015). Plap-1/asporin positively regulates FGF-2 activity. Journal of dental research, 94(10), 1417-1424. https://doi.org/10.1177/0022034515598507