Angiogenesis in the skin of SHARPIN-deficient mice with chronic proliferative dermatitis

Exp Mol Pathol. 2016 Dec;101(3):303-307. doi: 10.1016/j.yexmp.2016.05.015. Epub 2016 Oct 26.

Abstract

Angiogenesis is a common feature of pathological processes including wound healing, tumor formation, and chronic inflammation. Chronic inflammation can also be associated with dilation or proliferation of lymph vessels. We examined blood vessels and lymphatics and the expression of pro- and anti-angiogenic genes in the skin of SHARPIN-deficient mice which spontaneously develop a chronic proliferative dermatitis (cpdm). The number of blood vessels in the dermis of cpdm mice increased with age as the inflammation progressed. Lymphatics identified by labeling for LYVE1 and podoplanin were moderately dilated, but they were not increased in number. The expression of proangiogenic Vegfa, Flt1 and anti-angiogenic Sema3a mRNA was increased. VEGFA was primarily localized in keratinocytes of cpdm skin. There was also increased expression of Ece1 and Pdpn mRNA. Podoplanin was restricted to lymphatic endothelial cells in normal skin, but fibroblasts in cpdm skin also reacted with anti-podoplanin antibodies indicating that they were activated. The expression of other angiogenic and lymphangiogenic factors was not altered or decreased. These results indicate that cpdm mice may be a useful model to study the pathogenesis of angiogenesis in chronic inflammation.

Keywords: Angiogenesis; Dermatitis; Lymphangiogenesis; Podoplanin; VEGF.

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Dermatitis / metabolism*
  • Dermatitis / pathology
  • Endothelial Cells / metabolism
  • Endothelin-Converting Enzymes / genetics
  • Endothelin-Converting Enzymes / metabolism
  • Female
  • Fibroblasts / metabolism
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Keratinocytes / metabolism
  • Lymphatic Vessels / pathology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic / metabolism*
  • Semaphorin-3A / genetics
  • Semaphorin-3A / metabolism
  • Skin / blood supply*
  • Skin / cytology
  • Skin / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism

Substances

  • Carrier Proteins
  • Glycoproteins
  • Gp38 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Sema3a protein, mouse
  • Semaphorin-3A
  • Sipl1 protein, mouse
  • Vascular Endothelial Growth Factor A
  • Xlkd1 protein, mouse
  • Flt1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-1
  • Ece1 protein, mouse
  • Endothelin-Converting Enzymes