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

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 ne...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2013-02, Vol.110 (8), p.2852-2857
Hauptverfasser: Noda, Kazuo, Dabovic, Branka, Takagi, Kyoko, Inoue, Tadashi, Horiguchi, Masahito, Hirai, Maretoshi, Fujikawa, Yusuke, Akama, Tomoya O., Kusumoto, Kenji, Zilberberg, Lior, Sakai, Lynn Y., Koli, Katri, Naitoh, Motoko, von Melchner, Harald, Suzuki, Shigehiko, Rifkin, Daniel B., Nakamura, Tomoyuki
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Sprache:eng
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Zusammenfassung: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 culture medium promoted elastin deposition on microfibrils without 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1215779110