Nogo-B Promotes Angiogenesis in Proliferative Diabetic Retinopathy via VEGF/PI3K/Akt Pathway in an Autocrine Manner

Abstract

Background/Aims: Nogo-B, a conservative protein of endoplasmic reticulum, is a member of the reticulon family of proteins. Proliferative diabetic retinopathy (PDR) is the major concerning problem of diabetic retinopathy. This study explored the role of Nogo-B in the regulation of angiogenesis in PDR patients and primary human retinal endothelial cells (HRMECs). Methods: Nogo-B was down-regulated through the use of Lentivirus-NogoB-RNAi, the effects of Nogo-B on angiogenesis under high glucose stimulation were evaluated via CCK-8 assay, wound closure assay, transwell assay, and tube formation assay. Expression of Nogo-B, VEGF, PI3K and Akt were determined by western blotting, immunofluorescence, enzyme-linked immunosorbent assay (ELISA). Co-culture systerm was used to explore cell communication. Results: Nogo-B was highly enriched in ocular tissues of PDR patients and in HRMECs exposed to high glucose. Down-regulation of Nogo-B attenuated high glucose induced cell migration and tube formation in HRMECs. Mechanistically, in comparison with the negative control group, Lentivirus-NogoB-RNAi group had exhibited reduced VEGF secretion, weakened PI3K and Akt activation. Besides, high glucose treatment promoted the secretion of Nogo-B and presented as a “long-term memory”. Conclusions: These data collectively indicated that Nogo-B promoted angiogenesis in HRMECs via VEGF/PI3K/Akt pathway in an autocrine manner.

Imatinib Ameliorated Retinal Neovascularization by Suppressing PDGFR-α and PDGFR-β

“…Angiogenesis develops a neovascular network, which requires not only ECs but also the cooperation of PCs and SMCs [30,31]. The newly formed vessels were initiated by ECs and matured by PCs and SMCs.…”

Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells

“…Visual loss primarily occurs due to increased permeability of retinal vessels (diabetic macular edema) [3] and retinal neovascularization (proliferative diabetic retinopathy) [4,5]. As DR pathogenesis is multifactorial [6][7][8], precise molecular mechanisms therein are still not well understood.…”

Vascular endothelial growth factor A/Vascular endothelial growth factor receptor 2 axis promotes human dental pulp stem cell migration via the FAK/PI3K/Akt and p38 MAPK signalling pathways

“…The data demonstrated that phosphorylation of FAK was essential for the migration of hDPSCs, and this finding is in accordance with the role of FAK in MSCs . Previous studies have identified that the PI3K/Akt pathways induce proliferation and migration of various cells in response to VEGF (Zhang et al 2017, Huang et al 2018). Previous studies have identified that the PI3K/Akt pathways induce proliferation and migration of various cells in response to VEGF (Zhang et al 2017, Huang et al 2018).…”

“…PI3K participates widely in the multiple cell migration process by coordinating protein localization and conformation through activation or recruitment of pleckstrin homology domaincontaining proteins, including the protein kinase Akt (Lien et al 2017). Previous studies have identified that the PI3K/Akt pathways induce proliferation and migration of various cells in response to VEGF (Zhang et al 2017, Huang et al 2018). In the present study, wound healing assay and migration assays were performed with PI3K-specific inhibitors (LY294002) and Figure 5 VEGFA mediated migration of hDPSCs via VEGFR2 rather than VEGFR1 (a) After transfection with siVEGFR2 or siVEGFR1 for 48 h, hDPSCs were detected with Western blot and exposed to the indicated antibody.…”