Abstract
Background: Aberrant neovascularization resulting from inappropriate angiogenic signaling is closely related to many diseases, such as cancer, cardiovascular disease, and proliferative retinopathy. Although some factors involved in regulating pathogenic angiogenesis have been identified, the molecular mechanisms of proliferative retinopathy remain largely unknown. In the present study, we determined the role of platelet-derived growth factor-B (PDGF-B), one of the HIF-1-responsive gene products, in cell proliferation and angiogenesis in retinal microvascular endothelial cells (RMECs) and explored its regulatory mechanism.Methods: Cell counting kit-8 (CCK-8), bromodeoxyuridine (BrdU) incorporation, tube formation, cell migration, and Western blot assays were used in our study.Results: Our results showed that PDGF-B promoted cell proliferation and angiogenesis by increasing the activity of Src homology 2 domain-containing tyrosine phosphatase 2 (SHP-2) in RMECs, which was attenuated by the inhibition of PDGF receptor (PDGFR) or SHP-2 knockdown. Moreover, activation of c-Myc was involved in the processes of PDGF-B/SHP-2-driven cell proliferation in RMECs. The promoting effects of PDGF-B/SHP-2 on c-Myc expression were mediated by the Erk pathway.Conclusion: These results indicate that PDGF-B facilitates cell proliferation and angiogenesis, at least in part, via the SHP-2/Erk/c-Myc pathway in RMECs, implying new potential treatment candidates for retinal microangiopathy.
Highlights
Neovascularization is a multistep process, and a variety of growth factors are involved in regulating this process (Yang et al, 2016)
platelet-derived growth factor (PDGF)-B positively regulated the activation of c-Myc via the Src homology 2 domain-containing tyrosine phosphatase 2 (SHP-2)/Erk pathway in retinal microvascular endothelial cells (RMECs). These results indicate that platelet-derived growth factor-B (PDGF-B) facilitates cell proliferation, at least in part, via the SHP-2/Erk/c-Myc pathway, which provides potential treatment targets for retinal microangiopathy
Our results showed that treatment with PDGF-B led to increased cell viability, promoted the incorporation of BrdU into newly synthesized DNA, and induced the expression of Proliferating cell nuclear antigen (PCNA) in RMECs, which were mitigated by the inhibition of PDGF receptors (PDGFRs) (Figures 1A–C)
Summary
Neovascularization is a multistep process, and a variety of growth factors are involved in regulating this process (Yang et al, 2016). It is necessary to study the molecular mechanism regulating retinal angiogenesis. Increased expression of PDGF-B and its receptors is observed in the many proliferative retinal membranes (Robbins et al, 1994). The mechanism of PDGFB-regulated retinal angiogenesis remains to be elucidated. Some factors involved in regulating pathogenic angiogenesis have been identified, the molecular mechanisms of proliferative retinopathy remain largely unknown. We determined the role of platelet-derived growth factor-B (PDGF-B), one of the HIF-1-responsive gene products, in cell proliferation and angiogenesis in retinal microvascular endothelial cells (RMECs) and explored its regulatory mechanism
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