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Proteomics reveals ablation of PlGF increases antioxidant and neuroprotective proteins in the diabetic mouse retina


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Saddala, MS, Lennikov, A, Grab, DJ, Liu, G-S ORCID: 0000-0003-3379-724X, Tang, S and Huang, H 2018 , 'Proteomics reveals ablation of PlGF increases antioxidant and neuroprotective proteins in the diabetic mouse retina' , Scientific Reports, vol. 8, no. 1 , pp. 1-12 , doi: 10.1038/s41598-018-34955-x.

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Placental growth factor (PlGF or PGF), a member of the vascular endothelial growth factor (VEGF) sub-family, plays a crucial role in pathological angiogenesis and inflammation. However, the underlying molecular mechanisms that PlGF mediates regarding the complications of non-proliferative diabetic retinopathy (DR) remain elusive. Using an LC-MS/MS-based label-free quantification proteomic approach we characterized the alterations in protein expression caused by PlGF ablation in the retinas obtained from C57BL6, Akita, PlGF-/- and Akita.PlGF-/- mice. After extraction and enzymatic digestion with Trypsin/LysC, the retinal proteins were analyzed by Q-Exactive hybrid Quadrupole-Orbitrap mass spectrometry. Differentially expressed proteins (DEPs) were identified in four comparisons based on Z-score normalization and reproducibility by Pearson's correlation coefficient. The gene ontology (GO), functional pathways, and protein-protein network interaction analysis suggested that several proteins involved in insulin resistance pathways (Gnb1, Gnb2, Gnb4, Gnai2, Gnao1, Snap2, and Gngt1) were significantly down-regulated in PlGF ablated Akita diabetic mice (Akita.PlGF-/- vs. Akita) but up-regulated in Akita vs. C57 and PlGF-/- vs. C57 conditions. Two proteins involved in the antioxidant activity and neural protection pathways, Prdx6 and Map2 respectively, were up-regulated in the Akita.PlGF-/- vs. Akita condition. Overall, we predict that down-regulation of proteins essential for insulin resistance, together with the up-regulation of antioxidant and neuroprotection proteins highlight and epitomize the potential mechanisms important for future anti-PlGF therapies in the treatment of DR.

Item Type: Article
Authors/Creators:Saddala, MS and Lennikov, A and Grab, DJ and Liu, G-S and Tang, S and Huang, H
Keywords: diabetic retinopathy, placenta growth factor, proteomic
Journal or Publication Title: Scientific Reports
Publisher: Nature Publishing Group
ISSN: 2045-2322
DOI / ID Number: 10.1038/s41598-018-34955-x
Copyright Information:

Copyright 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

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