Secretogranin III promotes angiogenesis through MEK/ERK signaling pathway

Biochem Biophys Res Commun. 2018 Jan 1;495(1):781-786. doi: 10.1016/j.bbrc.2017.11.080. Epub 2017 Nov 14.

Abstract

Secretogranin III (Scg3) was recently discovered as the first highly diabetic retinopathy-associated angiogenic factor, and its neutralizing antibody alleviated the disease with high efficacy in diabetic mice. Investigation of its molecular mechanisms will facilitate the translation of this novel therapy. Scg3 was reported to induce the phosphorylation of mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK). Here we characterized the importance of MEK/ERK activation to Scg3 angiogenic activity. Our results showed that MEK inhibitor PD98059 blocked Scg3-induced proliferation of human umbilical vein endothelial cells (HUVECs). This finding was corroborated by PD98059 inhibition of HUVEC migration and tube formation. Furthermore, ERK inhibitor SCH772984 also suppressed Scg3-induced proliferation and migration of HUVECs. Taken together, these findings suggest that MEK-ERK pathway plays an important role in Scg3-induced angiogenesis.

Keywords: Angiogenesis; Angiogenic factor; ERK; MEK; Scg3; Secretogranin III.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenic Proteins / metabolism*
  • Cell Proliferation
  • Cells, Cultured
  • Chromogranins / metabolism*
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology*
  • Humans
  • MAP Kinase Signaling System*
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology*

Substances

  • Angiogenic Proteins
  • Chromogranins
  • SCG3 protein, human