Kōchi University

About: Kōchi University is a education organization based out in Kochi, Japan. It is known for research contribution in the topics: Population & Zircon. The organization has 5314 authors who have published 10056 publications receiving 204869 citations. The organization is also known as: Kōchi Daigaku.

Dysregulation of TGF-β1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice

Abstract: The core fucosylation (α1,6-fucosylation) of glycoproteins is widely distributed in mammalian tissues, and is altered under pathological conditions To investigate physiological functions of the core fucose, we generated α1,6-fucosyltransferase (Fut8)-null mice and found that disruption of Fut8 induces severe growth retardation and death during postnatal development Histopathological analysis revealed that Fut8-/- mice showed emphysema-like changes in the lung, verified by a physiological compliance analysis Biochemical studies indicated that lungs from Fut8-/- mice exhibit a marked overexpression of matrix metalloproteinases (MMPs), such as MMP-12 and MMP-13, highly associated with lung-destructive phenotypes, and a down-regulation of extracellular matrix (ECM) proteins such as elastin, as well as retarded alveolar epithelia cell differentiation These changes should be consistent with a deficiency in TGF-β1 signaling, a pleiotropic factor that controls ECM homeostasis by down-regulating MMP expression and inducing ECM protein components In fact, Fut8-/- mice have a marked dysregulation of TGF-β1 receptor activation and signaling, as assessed by TGF-β1 binding assays and Smad2 phosphorylation analysis We also show that these TGF-β1 receptor defects found in Fut8-/- cells can be rescued by reintroducing Fut8 into Fut8-/- cells Furthermore, exogenous TGF-β1 potentially rescued emphysema-like phenotype and concomitantly reduced MMP expression in Fut8-/- lung We propose that the lack of core fucosylation of TGF-β1 receptors is crucial for a developmental and progressive/destructive emphysema, suggesting that perturbation of this function could underlie certain cases of human emphysema