Latent TGF-β binding protein 2 and 4 have essential overlapping functions in microfibril development

  • Microfibrils are exracellular matrix components necessary for elastic fiber assembly and for suspending lenses. We previously reported that latent TGF-β binding protein 2 (LTBP-2), a microfibril-associated protein, is required for forming stable microfibril bundles in ciliary zonules. However, it was not understood why Ltbp2 null mice only showed an eye-specific phenotype, whereas LTBP-2 is abundantly expressed in other tissues containing microfibrils in wild type mice. Here, we show that LTBP-4, another microfibril-associated protein, compensates for the loss of LTBP-2 in microfibril formation. Ltbp2/4S double knockout (DKO) mice showed increased lethality due to emphysema, which was much more severe than that found in Ltbp4S null mice. Elastic fibers in the lungs of Ltbp2/4S DKO mice were severely disorganized and fragmented. Cultured mouse embryonic fibroblasts (MEFs) from Ltbp2/4S DKO embryos developed reduced microfibril meshwork in serum-free conditions, whereas the microfibril formation was restored by the addition of either recombinant LTBP-2 or -4. Finally, ectopic expression of LTBP-4 in the whole body restored ciliary zonule microfibril bundles in the eyes of Ltbp2 null mice. These data suggest that LTBP-2 and -4 have critical overlapping functions in forming the robust structure of microfibrils in vitro and in vivo.

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Author:Yusuke Fujikawa, Hideyuki Yoshida, Tadashi Inoue, Tetsuya Ohbayashi, Kazuo Noda, Harald von Melchner, Toshiji Iwasaka, Ichiro Shiojima, Tomoya O. Akama, Tomoyuki Nakamura
Pubmed Id:
Parent Title (English):Scientific reports
Publisher:Macmillan Publishers Limited, part of Springer Nature
Place of publication:[London]
Document Type:Article
Year of Completion:2017
Date of first Publication:2017/03/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/12/18
Tag:Developmental biology; Molecular biology
Issue:Art. 43714
Page Number:10
First Page:1
Last Page:10
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Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0