The biomechanical properties of an epithelial tissue determine the location of its vasculature

Nat Commun. 2016 Dec 20:7:13560. doi: 10.1038/ncomms13560.

Abstract

An important question is how growing tissues establish a blood vessel network. Here we study vascular network formation in pancreatic islets, endocrine tissues derived from pancreatic epithelium. We find that depletion of integrin-linked kinase (ILK) in the pancreatic epithelial cells of mice results in glucose intolerance due to a loss of the intra-islet vasculature. In turn, blood vessels accumulate at the islet periphery. Neither alterations in endothelial cell proliferation, apoptosis, morphology, Vegfa expression and VEGF-A secretion nor 'empty sleeves' of vascular basement membrane are found. Instead, biophysical experiments reveal that the biomechanical properties of pancreatic islet cells, such as their actomyosin-mediated cortex tension and adhesive forces to endothelial cells, are significantly changed. These results suggest that a sorting event is driving the segregation of endothelial and epithelial cells and indicate that the epithelial biomechanical properties determine whether the blood vasculature invades or envelops a growing epithelial tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / physiology
  • Animals
  • Basement Membrane / physiology
  • Biomechanical Phenomena
  • Cell Adhesion / physiology
  • Endothelial Cells / cytology
  • Endothelial Cells / physiology
  • Epithelial Cells / physiology
  • Epithelium / blood supply*
  • Epithelium / physiology*
  • Female
  • Glucose Intolerance / physiopathology
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / blood supply*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neovascularization, Physiologic
  • Protein Serine-Threonine Kinases / deficiency
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Insulin
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Actomyosin
  • integrin-linked kinase
  • Protein Serine-Threonine Kinases