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

First Author  Noda K Year  2013
Journal  Proc Natl Acad Sci U S A Volume  110
Issue  8 Pages  2852-7
PubMed ID  23382201 Mgi Jnum  J:194311
Mgi Id  MGI:5473427 Doi  10.1073/pnas.1215779110
Citation  Noda K, et al. (2013) Latent TGF-beta binding protein 4 promotes elastic fiber assembly by interacting with fibulin-5. Proc Natl Acad Sci U S A 110(8):2852-7
abstractText  Elastic fiber assembly requires deposition of elastin monomers onto microfibrils, the mechanism of which is incompletely understood. Here we show that latent TGF-beta 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-beta because TGF-beta-free recombinant LTBP-4 was as potent an elastogenic inducer as TGF-beta-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.
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