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Retinal pigment epithelium‐derived transforming growth factor‐β2 inhibits the angiogenic response of endothelial cells by decreasing vascular endothelial growth factor receptor‐2 expression
Author(s) -
Jeong HanSeok,
Yun JangHyuk,
Lee DaHye,
Lee Eun Hui,
Cho ChungHyun
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27156
Subject(s) - microbiology and biotechnology , transforming growth factor , angiogenesis , vascular endothelial growth factor , retinal pigment epithelium , endothelial stem cell , biology , growth factor , vascular endothelial growth factor b , cytokine , kinase insert domain receptor , vascular endothelial growth factor a , vascular endothelial growth factor c , chemistry , receptor , retinal , cancer research , immunology , vegf receptors , biochemistry , in vitro
Transforming growth factor‐β (TGF‐β) is a multifunctional cytokine that is known to modulate various aspects of endothelial cell (EC) biology. Retinal pigment epithelium (RPE) is important for regulating angiogenesis of choriocapillaris and one of the main cell sources of TGF‐β secretion, particularly TGF‐β2. However, it is largely unclear whether and how TGF‐β2 affects angiogenic responses of ECs. In the current study, we demonstrated that TGF‐β2 reduces vascular endothelial growth factor receptor‐2 (VEGFR‐2) expression in ECs and thereby inhibits vascular endothelial growth factor (VEGF) signaling and VEGF‐induced angiogenic responses such as EC migration and tube formation. We also demonstrated that the reduction of VEGFR‐2 expression by TGF‐β2 is due to the suppression of JNK signaling. In coculture of RPE cells and ECs, RPE cells decreased VEGFR‐2 levels in ECs and EC migration. In addition, we showed that TGF‐β2 derived from RPE cells is involved in the reduction of VEGFR‐2 expression and inhibition of EC migration. These results suggest that TGF‐β2 plays an important role in inhibiting the angiogenic responses of ECs during the interaction between RPE cells and ECs and that angiogenic responses of ECs may be amplified by a decrease in TGF‐β2 expression in RPE cells under pathologic conditions.