title: Latent TGF-β binding protein 4 promotes elastic fiber assembly by interacting with fibulin-5.
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 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.
authors: Department of Pharmacology,  Kansai Medical University, Moriguchi City, Osaka 570-8506,  Japan.
authors: Kazuo
authors: K
authors: Noda
authors: Branka
authors: B
authors: Dabovic
authors: Kyoko
authors: K
authors: Takagi
authors: Tadashi
authors: T
authors: Inoue
authors: Masahito
authors: M
authors: Horiguchi
authors: Maretoshi
authors: M
authors: Hirai
authors: Yusuke
authors: Y
authors: Fujikawa
authors: Tomoya O
authors: TO
authors: Akama
authors: Kenji
authors: K
authors: Kusumoto
authors: Lior
authors: L
authors: Zilberberg
authors: Lynn Y
authors: LY
authors: Sakai
authors: Katri
authors: K
authors: Koli
authors: Motoko
authors: M
authors: Naitoh
authors: Harald
authors: H
authors: von Melchner
authors: Shigehiko
authors: S
authors: Suzuki
authors: Daniel B
authors: DB
authors: Rifkin
authors: Tomoyuki
authors: T
authors: Nakamura
mesh_terms: D000818:Animals; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; C120769:Fbln5 protein, mouse; D053779:Latent TGF-beta Binding Proteins; D011994:Recombinant Proteins
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