Abstract

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.

Details

Title
Proteomics reveals ablation of PlGF increases antioxidant and neuroprotective proteins in the diabetic mouse retina
Author
Saddala, Madhu Sudhana 1 ; Lennikov, Anton 2   VIAFID ORCID Logo  ; Grab, Dennis J 3 ; Liu, Guei-Sheung 4   VIAFID ORCID Logo  ; Tang, Shibo 5 ; Huang, Hu 6 

1  Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States of America 
2  Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States of America; School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia 
3  The Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America; The Department of Pathology, Johns Hopkins University, Baltimore, Maryland, United States of America 
4  Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia 
5  Aier School of Ophthalmology, Central South University, Changsha, Hunan, China; Aier Eye Institute, Changsha, Hunan, China 
6  Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States of America; Aier School of Ophthalmology, Central South University, Changsha, Hunan, China; Aier Eye Institute, Changsha, Hunan, China 
Pages
1-12
Publication year
2018
Publication date
Nov 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-34955-x
ProQuest document ID
2132701978
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.