Placental growth factor stabilizes VEGF receptor-2 protein in retinal pigment epithelial cells by downregulating glycogen synthase kinase 3 activity

Murata, Miyuki; Noda, Kousuke; Kase, Satoru; Hase, Keitaro; Wu, Di; Andõ, Ryõ; Ishida, Susumu

doi:10.1016/j.jbc.2022.102378

Cited by 5 publications

(4 citation statements)

References 30 publications

(53 reference statements)

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“…Long-term anti-VEGF-A suppression appears to induce atrophy of retinal pigment epithelium (RPE), triggers apoptosis, and heightens cellular vulnerability to oxidative stress [ 27 ], which are now recognized as key pathogenic events in vitreoretinal disorders [ 1 , 28 ]. On the other hand, PlGF plays a protective role for RPE cells, shielding them from apoptosis induced by serum starvation and maintaining the stability of VEGFR-2 in RPE [ 29 ]. Knocking down PlGF leads to VEGFR-2 protein instability, disrupting the signal transmission of the VEGFA/VEGFR-2 pathway and diminishing the protective effect of VEGF-A in RPE cells.…”

Section: Discussionmentioning

confidence: 99%

“…Knocking down PlGF leads to VEGFR-2 protein instability, disrupting the signal transmission of the VEGFA/VEGFR-2 pathway and diminishing the protective effect of VEGF-A in RPE cells. Consequently, long-term VEGF-A inhibition in patients with neovascular age-related macular degeneration (AMD) may contribute to macular atrophy and could impact PlGF [ 29 ]. On the other hand, several implied that PlGF plays a role in subretinal fibrosis and that anti-PlGF can help ameliorate the associated symptoms.…”

Section: Discussionmentioning

confidence: 99%

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Serum and Vitreous Levels of Placenta Growth Factor in Diabetic Retinopathy Patients: Correlation With Disease Severity and Optical Coherence Tomographic Parameters

Mesquita,

Santos,

Sousa

et al. 2024

Cureus

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Purpose The primary objective of this study was to compare placenta growth factor (PlGF) levels in the serum and vitreous of diabetic retinopathy (DR) patients to non-diabetic controls. Additionally, the study aimed to establish associations between serum and vitreous PlGF concentrations and to examine the correlation between vitreous PlGF in DR patients and morphological parameters. Methods This study included serum and vitreous samples from 38 patients, including 21 patients with DR and 17 non-diabetic controls. The control group included non-diabetic patients with rhegmatogenous retinal detachment with retinal tears secondary to posterior vitreous detachment or trauma. PlGF levels were quantified in vitreous and serum samples using an enzyme-linked immunosorbent assay (ELISA). Optical coherence tomography (OCT) scans from DR patients were evaluated to measure the central retinal thickness (CRT) and macular volume (MV). Results DR patients had significantly higher mean vitreous PlGF levels compared to non-DR patients (70.0±39.2 vs. 46.47±9.7 pg/mL, p-value=0.004). However, no significant increase in mean serum PlGF levels was observed in DR patients (p-value=0.232). Within the DR group, proliferative DR (PDR) patients presented significantly higher vitreous PlGF levels than non-PDR (NPDR) patients (76.5±41.0 vs. 42.5±5.0 pg/mL, p-value=0.009). There was no association between serum and vitreous PlGF levels. The correlation between vitreous PlGF levels and morphological parameters was r sp =0.175, p-value=0.488 for CRT, and r sp =0.288, p-value=0.262 for MV. Conclusion This study emphasizes the important role of PlGF in neovascularization, specifically highlighting its overexpression exclusively in vitreous from PDR patients. The observed increase in PlGF levels may be indicative of disease severity. The lack of correlation between vitreous and serum PlGF levels suggests a potential dissociation between intravitreal and systemic PlGF synthesis. Consequently, targeting PlGF in therapeutic approaches may offer an additional strategy for ocular pathologies with a neovascular component.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Serum and Vitreous Levels of Placenta Growth Factor in Diabetic Retinopathy Patients: Correlation With Disease Severity and Optical Coherence Tomographic Parameters

Mesquita,

Santos,

Sousa

et al. 2024

Cureus

View full text Add to dashboard Cite

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“…Macrophages also facilitate the migration of choroidal capillaries by eroding already thinned bruch membrane with proteolytic enzymes (13). In AMD, increased VEGF was demonstrated in RPE cells (14). VEGF has functions in paracrine signal transmission between RPE and choriocapillaris and in the continuation of fenestrated structure of choriocapillaris (15).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Photodynamic Therapy-Combined Intravitreal Bevacizumab in Age Related Macular Degeneration

Pangal,

Özkırış

2024

Journal of Anatolian Medical Research

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Aim: It was aimed to compare treatment results of photodynamic therapy (PDT) and PDT-combined intravitreal bevacizumab injection (PDT+IVB) in patients with age-related macular degeneration (AMD). Material and Methods: 63 eyes of 55 patients with neovascular AMD were included. Group 1 consisted of 40 eyes of 35, group 2 consisted of 23 eyes of 20 patients. Visual acuity (VA), intraocular pressure measurement and fundus examination were performed. Pattern Electroretinography P50 amplitude and edema map values (EMV) were measured with Heidelberg Retina Tomograph (HRTII). Results: VA increased in 14, remained unchanged in 17, decreased in 9 eyes in Group 1 (PDT). The PERG P50 amplitudes were compared with values of pre-treatment, and found increased as 10.6%, 11.98%, and 8.46% and HRTII EMV were 5.86%, 4.88%, and 11.22% at 1st, 3rd, and 6th months, respectively. In Group 2 (PDT+IVB), VA improved in 9, remained unchanged in 8, decreased in 6 eyes. PERG P50 amplitudes were decreased as 10.15%, 5.8%, and 0.1% and HRTII EMV were decreased as 13.07%, 12.17%, and 14.87% at 1st, 3rd, and 6th months, respectively. Conclusion: Verteporfin and PDT are effective and safe methods that preserve VA in subfoveal choroidal neovascular membranes due to neovascular AMD.

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“…Besides, the ligands bind to VEGFR-2 which triggers the pathways of migration, vascular permeability, endothelial cell proliferation, and survival (Masoumi Moghaddam et al 2012;de Vries et al 2019;Murata et al 2022). In the results, we suggested VEGF-165…”

Section: The Transplantation Platform Shows No Effect On Insulin-depe...mentioning

confidence: 99%

Establishment of transplantation platform for delivering mouse induced pluripotent stem cell-derived insulin-producing cells (mips-ipcs) for diabetes treatment

Tran

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Pancreatic beta-cell replacement is recognized for feasible type 1 diabetes (T1D) treatment. However, in post-transplantation, the autoimmune destruction incidentally attacks the activity and survival of beta-cells are reported in animal and human. To address these concerns, the generation of immortalized, biocompatible beta-cells,�and the engraftment platform are insightfully investigated.�The stepwise chemical process was used for�in vitro�Insulin-producing cells (IPCs) production from�mouse gingival fibroblast-induced pluripotent stem cells (mGF-iPSCs). The real-time qRT-PCR, glucose stimulation C-peptide/Insulin�secretion, immunostaining, and visible cell methods were examined during IPC differentiation. The�encapsulated-IPC�beads�were�loaded into subcutaneous�pocket�space via transplantation platform. Completed blood count, blood chemistry,�C-peptide,�HOMA indexes,�intraperitoneal glucose tolerance test,�and histopathology were analyzed at pre-, post-transplantation and at termination. The 40 cytokines were explored via�antibody�array detection.�In this study,�in vitro�IPC differentiation protocol�wasperceptively dissection. IPC encapsulation achieved to the transplantable capacity.In mice, the�catheter insertion and 10%�Pluronic-F127 carrying-VEGF-165�(VP) created the�subcutaneous pocket formation (SPF), and stimulated angiogenesis and neovascularization surrounding the SPF.�Especially,�IPC-bead�engraftment�alleviated�hyperglycemia in�STZ-induced-diabetic mice-VP + IPC-bead transplantation.�In post-transplantation,�IPC-bead�transplantation�showed noimmune�response, as well as, IPC-bead maintained the health condition in diabetic mice.�The obtained results�can be�applied as a clinical transplantation protocol for T1D treatment using cell-based therapy.

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Placental growth factor stabilizes VEGF receptor-2 protein in retinal pigment epithelial cells by downregulating glycogen synthase kinase 3 activity

Cited by 5 publications

References 30 publications

Serum and Vitreous Levels of Placenta Growth Factor in Diabetic Retinopathy Patients: Correlation With Disease Severity and Optical Coherence Tomographic Parameters

Serum and Vitreous Levels of Placenta Growth Factor in Diabetic Retinopathy Patients: Correlation With Disease Severity and Optical Coherence Tomographic Parameters

Evaluation of Photodynamic Therapy-Combined Intravitreal Bevacizumab in Age Related Macular Degeneration

Establishment of transplantation platform for delivering mouse induced pluripotent stem cell-derived insulin-producing cells (mips-ipcs) for diabetes treatment

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