bims-stacyt Biomed news
on Paracrine crosstalk between cancer and the organism
Issue of 2018‒12‒16
two papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge


  1. Front Endocrinol (Lausanne). 2018 ;9 708
    Krick S, Helton ES, Hutcheson SB, Blumhof S, Garth JM, Denson RS, Zaharias RS, Wickham H, Barnes JW.
      The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins. The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation. In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Here, we demonstrate that FGF23 increased the O-GlcNAc modification of proteins in HBECs. Furthermore, the increase in O-GlcNAc levels by FGF23 stimulation resulted in the downstream activation of NFAT and secretion of interleukin-6 (IL-6). Conversely, inhibition of FGF23 signaling and/or O-GlcNAc transferase (OGT)/O-GlcNAc reversed these effects. Collectively, these data suggest that FGF23 induced IL-6 upregulation and secretion is, at least, partially mediated via the activation of the HBP and O-GlcNAc levels in HBECs. These findings identify a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs. The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
    Keywords:  FGF23 = fibroblast growth factor 23; IL-6 (Interleukin 6); NFAT (nuclear factor expression of activated T cell); O-GlcNAc; inflammation
    DOI:  https://doi.org/10.3389/fendo.2018.00708
  2. iScience. 2018 Nov 23. pii: S2589-0042(18)30225-6. [Epub ahead of print]10 211-221
    Sasaoka N, Imamura H, Kakizuka A.
      Milk sugar is composed of glucose and galactose. Galactose is less suitable as an energy source than glucose. Thus, it has been a puzzle as to why mammals utilize galactose as a major component of milk sugar. Here we show that in hypoglycemic conditions, the presence of a trace amount of galactose, but not glucose, is able to maintain the production of mature glycoproteins and to abolish cell-death-inducing endoplasmic reticulum stress. In severely sugar-limited conditions, both glucose and galactose enter into the glycolytic pathway, but galactose is not able to raise the phosphofructokinase 1 activity, leading to the accumulation of fructose-6-phosphate, which in turn is utilized for the maturation of glycoproteins (e.g., growth factor receptors) and allows the activation of their intracellular signaling and prevents cell death from hypoglycemic conditions. Thus trace amounts of galactose may play unexpectedly important roles in the growth of infants and their protection during starvation.
    Keywords:  Cell Biology; Physiology
    DOI:  https://doi.org/10.1016/j.isci.2018.11.035