SHP-2-Induced Activation of c-Myc Is Involved in PDGF-B-Regulated Cell Proliferation and Angiogenesis in RMECs
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 molecul...
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2020.555006/full |
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| author | Jun Ma Jun Ma Wenyi Tang Ruiping Gu Fangyuan Hu Fangyuan Hu Lei Zhang Jihong Wu Jihong Wu Gezhi Xu Gezhi Xu |
| author_facet | Jun Ma Jun Ma Wenyi Tang Ruiping Gu Fangyuan Hu Fangyuan Hu Lei Zhang Jihong Wu Jihong Wu Gezhi Xu Gezhi Xu |
| author_sort | Jun Ma |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T02:03:48Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-12T02:03:48Z |
| publishDate | 2020-11-01 |
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| series | Frontiers in Physiology |
| spelling | doaj.art-3089284b93384566931ded56eac0edde2022-12-22T00:42:06ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-11-011110.3389/fphys.2020.555006555006SHP-2-Induced Activation of c-Myc Is Involved in PDGF-B-Regulated Cell Proliferation and Angiogenesis in RMECsJun Ma0Jun Ma1Wenyi Tang2Ruiping Gu3Fangyuan Hu4Fangyuan Hu5Lei Zhang6Jihong Wu7Jihong Wu8Gezhi Xu9Gezhi Xu10Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, ChinaDepartment of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, ChinaDepartment of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, ChinaEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, ChinaDepartment of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, ChinaDepartment of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fphys.2020.555006/fullretinaproliferationangiogenesisPDGF-BSHP-2 |
| spellingShingle | Jun Ma Jun Ma Wenyi Tang Ruiping Gu Fangyuan Hu Fangyuan Hu Lei Zhang Jihong Wu Jihong Wu Gezhi Xu Gezhi Xu SHP-2-Induced Activation of c-Myc Is Involved in PDGF-B-Regulated Cell Proliferation and Angiogenesis in RMECs Frontiers in Physiology retina proliferation angiogenesis PDGF-B SHP-2 |
| title | SHP-2-Induced Activation of c-Myc Is Involved in PDGF-B-Regulated Cell Proliferation and Angiogenesis in RMECs |
| title_full | SHP-2-Induced Activation of c-Myc Is Involved in PDGF-B-Regulated Cell Proliferation and Angiogenesis in RMECs |
| title_fullStr | SHP-2-Induced Activation of c-Myc Is Involved in PDGF-B-Regulated Cell Proliferation and Angiogenesis in RMECs |
| title_full_unstemmed | SHP-2-Induced Activation of c-Myc Is Involved in PDGF-B-Regulated Cell Proliferation and Angiogenesis in RMECs |
| title_short | SHP-2-Induced Activation of c-Myc Is Involved in PDGF-B-Regulated Cell Proliferation and Angiogenesis in RMECs |
| title_sort | shp 2 induced activation of c myc is involved in pdgf b regulated cell proliferation and angiogenesis in rmecs |
| topic | retina proliferation angiogenesis PDGF-B SHP-2 |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2020.555006/full |
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