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

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posted on 2023-05-19, 23:20 authored by Saddala, MS, Lennikov, A, Grab, DJ, Guei-Sheung LiuGuei-Sheung Liu, Tang, S, Huang, H
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.

History

Publication title

Scientific Reports

Volume

8

Article number

16728

Number

16728

Pagination

1-12

ISSN

2045-2322

Department/School

Menzies Institute for Medical Research

Publisher

Nature Publishing Group

Place of publication

United Kingdom

Rights statement

Copyright 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified; Expanding knowledge in the health sciences

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