Latent TGF-β binding protein 4 promotes elastic fiber assembly by interacting with fibulin-5

Kazuo Noda, Branka Dabovic, Kyoko Takagi, Tadashi Inoue, Masahito Horiguchi, Maretoshi Hirai, Yusuke Fujikawa, Tomoya O. Akama, Kenji Kusumoto, Lior Zilberberg, Lynn Y. Sakai, Katri Koli, Motoko Naitoh, Harald Von Melchner, Shigehiko Suzuki, Daniel B. Rifkin, Tomoyuki Nakamura

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Elastic fiber assembly requires deposition of elastin monomers onto microfibrils, the mechanism of which is incompletely understood. Here we show that latent TGF-β binding protein 4 (LTBP-4) potentiates formation of elastic fibers through interacting with fibulin-5, a tropoelastin-binding protein necessary for elastogenesis. Decreased expression of LTBP-4 in human dermal fibroblast cells by siRNA treatment abolished the linear deposition of fibulin-5 and tropoelastin on microfibrils. It is notable that the addition of recombinant LTBP-4 to cell culturemediumpromoted elastin deposition onmicrofibrilswithout changing the expression of elastic fiber components. This elastogenic property of LTBP-4 is independent of bound TGF-β because TGF-β-free recombinant LTBP-4 was as potent an elastogenic inducer as TGF-β-bound recombinant LTBP-4. Without LTBP-4, fibulin-5 and tropoelastin deposition was discontinuous and punctate in vitro and in vivo. These data suggest a unique function for LTBP-4 during elastic fibrogenesis, making it a potential therapeutic target for elastic fiber regeneration.

Original languageEnglish (US)
Pages (from-to)2852-2857
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number8
DOIs
StatePublished - Feb 19 2013

Keywords

  • Connective tissue
  • Development
  • Extracellular matrix

ASJC Scopus subject areas

  • General

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  • Cite this

    Noda, K., Dabovic, B., Takagi, K., Inoue, T., Horiguchi, M., Hirai, M., Fujikawa, Y., Akama, T. O., Kusumoto, K., Zilberberg, L., Sakai, L. Y., Koli, K., Naitoh, M., Von Melchner, H., Suzuki, S., Rifkin, D. B., & Nakamura, T. (2013). Latent TGF-β binding protein 4 promotes elastic fiber assembly by interacting with fibulin-5. Proceedings of the National Academy of Sciences of the United States of America, 110(8), 2852-2857. https://doi.org/10.1073/pnas.1215779110