2. Academic Validation
  3. FN-EDA mediates angiogenesis of hepatic fibrosis via integrin-VEGFR2 in a CD63 synergetic manner

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

  • Cell Death Discov. 2020 Dec 8;6(1):140. doi: 10.1038/s41420-020-00378-9.
Xiaonan Su 1 2,  Xiaowen Ma 1 2,  Xiaoyu Xie 1 2,  Hao Wu 1 3,  Le Wang 1 3,  Yuemin Feng 1 3,  Zhen Yu 1 2,  Chenxi Liu 1 2,  Jianni Qi 4 5,  Qiang Zhu 6 7 8
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
  • 2 Shandong Provincial Engineering and Technological Research Center for Liver Diseases Prevention and Control, Jinan, 250021, Shandong, China.
  • 3 Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
  • 4 Shandong Provincial Engineering and Technological Research Center for Liver Diseases Prevention and Control, Jinan, 250021, Shandong, China. slqijn@126.com.
  • 5 Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China. slqijn@126.com.
  • 6 Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. zhuqiang@sdu.edu.cn.
  • 7 Shandong Provincial Engineering and Technological Research Center for Liver Diseases Prevention and Control, Jinan, 250021, Shandong, China. zhuqiang@sdu.edu.cn.
  • 8 Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. zhuqiang@sdu.edu.cn.
PMID: 33293521 DOI: 10.1038/s41420-020-00378-9
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/KDR/Flk-1 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.

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