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

野田, 和男, Yoshida, Hideyuki, Inoue, Tadashi, Ohbayashi, Tetsuya, Noda, Kazuo, von Melchner, Harald, Iwasaka, Toshiji, Shiojima, Ichiro, Akama, Tomoya O., Nakamura, Tomoyuki

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.

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

抄録

収録刊行物

キーワード

詳細情報詳細情報について

書き出し

問題の指摘

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

抄録

収録刊行物

キーワード

詳細情報 詳細情報について

書き出し

問題の指摘

参加プロジェクトリスト

詳細情報詳細情報について