Mechanisms of pulmonary fibrosis induced by core fucosylation in pericytes

Int J Biochem Cell Biol. 2017 Jul:88:44-54. doi: 10.1016/j.biocel.2017.05.010. Epub 2017 May 5.

Abstract

Pulmonary fibrosis is a common outcome of a variety of pulmonary interstitial diseases, and myofibroblasts are the main culprit for this process. Recent studies have found that pericytes are one of the major sources of myofibroblasts; the transformation of which involves a complex process of activation of TGF-β/Smad2/3 and PDGFβ/Erk signaling pathways. We have reported that the transforming growth factor-β receptor and platelet-derived growth factor-β receptor (TGF-βR I and PDGFβR, respectively) are modified by glycosylation. Thus, we hope to regulate the above-mentioned signal pathways through core fucosylation (CF) catalyzed by α-1,6-fucosyltransferase (FUT8). Previous work has confirmed that TGF-β1 can induce the transformation of pericytes into myofibroblasts, while FUT8siRNA can inhibit such transformation. In the present study, we used an adenovirus packaging FUT8 shRNA to infect a bleomycin-induced pulmonary fibrosis mouse model and determined the effect of CF on pulmonary fibrosis by analyzing the mechanism of CF-mediated pericyte transformation. Our findings may shed new light on the mechanism of pulmonary interstitial fibrosis and provide a novel therapeutic target for clinical applications.

Keywords: Core fucosylation; FUT8; Myofibroblasts; Pericyte; Pulmonary fibrosis.

MeSH terms

  • Animals
  • Bleomycin / pharmacology
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Fucose / metabolism*
  • Fucosyltransferases / deficiency
  • Fucosyltransferases / genetics
  • Gene Expression Regulation / drug effects
  • Gene Knockdown Techniques
  • Glycosylation / drug effects
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pericytes / drug effects
  • Pericytes / metabolism*
  • Pericytes / pathology
  • Protein Serine-Threonine Kinases / metabolism
  • Pulmonary Fibrosis / genetics
  • Pulmonary Fibrosis / metabolism*
  • Pulmonary Fibrosis / pathology*
  • RNA, Small Interfering / genetics
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / metabolism
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / pharmacology

Substances

  • RNA, Small Interfering
  • Receptors, Transforming Growth Factor beta
  • Smad2 Protein
  • Smad3 Protein
  • Transforming Growth Factor beta1
  • Bleomycin
  • Fucose
  • Fucosyltransferases
  • Glycoprotein 6-alpha-L-fucosyltransferase
  • Receptor, Platelet-Derived Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I