Cell Death Discovery (Dec 2020)

FN-EDA mediates angiogenesis of hepatic fibrosis via integrin-VEGFR2 in a CD63 synergetic manner

  • Xiaonan Su,
  • Xiaowen Ma,
  • Xiaoyu Xie,
  • Hao Wu,
  • Le Wang,
  • Yuemin Feng,
  • Zhen Yu,
  • Chenxi Liu,
  • Jianni Qi,
  • Qiang Zhu

DOI
https://doi.org/10.1038/s41420-020-00378-9
Journal volume & issue
Vol. 6, no. 1
pp. 1 – 14

Abstract

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Abstract Pathological angiogenesis is an important component of hepatic fibrosis along with fibrous deposition, but its role is not well understood. Here, we demonstrated that fibronectin containing extra domain A(FN-EDA), a fibronectin splice variant highly expressed in hepatic fibrosis, mediated angiogenesis in disease progression. FN-EDA was positively correlated with pathological angiogenesis in hepatic fibrosis, and a reduction in FN-EDA expression was associated with diminished intrahepatic angiogenesis and fibrosis. FN-EDA mostly colocalized with hepatic stellate cells (HSCs) and interference or blockage of FN-EDA attenuated migration and tube formation in co-cultured endothelial cells. Mechanistic studies indicated that FN-EDA was secreted to promote phosphorylation of VEGFR2 with the assistance of integrin and CD63. Targeting FN-EDA-integrin combination postponed the progression of hepatic angiogenesis and fibrosis in vivo. These results indicated that FN-EDA plays an emerging role in angiogenesis in hepatic fibrosis and could be a potential therapeutic intervention for the disease.