Vascular endothelial growth factor-D mediates fibrogenic response in myofibroblasts

Tieqiang Zhao, Wenyuan Zhao, Weixin Meng, Chang Liu, Yuanjian Chen, Syamal Bhattacharya, Yao Sun

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF)-D is a crucial mediator of angiogenesis. Following myocardial infarction (MI), cardiac VEGF-D and VEGF receptor (VEGFR)-3 are significantly upregulated. In addition to endothelial cells, myofibroblasts at the site of MI highly express VEGFR-3, implicating the involvement of VEGF-D in cardiac fibrogenesis that promotes repair and remodeling. The aim of the current study was to further explore the critical role of VEGF-D in fibrogenic response in myofibroblasts. Myofibroblast proliferation, migration, collagen synthesis, and degradation were investigated in cultured cardiac myofibroblasts subjected to VEGF-D with/without VEGFR antagonist or ERK inhibitor. Vehicle-treated cells served as controls. Myofibroblast proliferation and migration were detected by BrdU assay and Boyden Chamber method, respectively. Expression of type I collagen, metalloproteinase (MMP)-2/-9, tissue inhibitor of MMP (TIMP)-1/-2, and ERK phosphorylation were evaluated by Western blot analyses. Our results revealed that compared to controls, (1) VEGF-D significantly increased myofibroblast proliferation and migration; (2) VEGF-D significantly upregulated type I collagen synthesis in a dose- and time-dependent manner; (3) VEGFR antagonist abolished VEGF-D-induced myofibroblast proliferation and type I collagen release; (4) VEGF-D stimulated MMP-2/-9 and TIMP-1/-2 synthesis; (5) VEGF-D activated ERK phosphorylation; and (6) ERK inhibitor abolished VEGF-D-induced myofibroblast proliferation and type I collagen synthesis. Our in vitro studies have demonstrated that VEGF-D serves as a crucial profibrogenic mediator by stimulating myofibroblast growth, migration and collagen synthesis. Further studies are underway to determine the role of VEGF-D in fibrous tissue formation during cardiac repair following MI.

Original languageEnglish (US)
Pages (from-to)127-135
Number of pages9
JournalMolecular and Cellular Biochemistry
Volume413
Issue number1-2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Vascular Endothelial Growth Factor D
Myofibroblasts
Collagen Type I
Phosphorylation
Matrix Metalloproteinase Inhibitors
Myocardial Infarction
Tissue
Repair
Collagen
Vascular Endothelial Growth Factor Receptor-3
Vascular Endothelial Growth Factor Receptor
Matrix Metalloproteinase 2
Endothelial cells
Matrix Metalloproteinase 9
Bromodeoxyuridine
Matrix Metalloproteinases

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Vascular endothelial growth factor-D mediates fibrogenic response in myofibroblasts. / Zhao, Tieqiang; Zhao, Wenyuan; Meng, Weixin; Liu, Chang; Chen, Yuanjian; Bhattacharya, Syamal; Sun, Yao.

In: Molecular and Cellular Biochemistry, Vol. 413, No. 1-2, 01.02.2016, p. 127-135.

Research output: Contribution to journalArticle

Zhao, Tieqiang ; Zhao, Wenyuan ; Meng, Weixin ; Liu, Chang ; Chen, Yuanjian ; Bhattacharya, Syamal ; Sun, Yao. / Vascular endothelial growth factor-D mediates fibrogenic response in myofibroblasts. In: Molecular and Cellular Biochemistry. 2016 ; Vol. 413, No. 1-2. pp. 127-135.
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