Preprint Article Version 1 This version is not peer-reviewed

Pathway-Focused Gene Interaction Analysis Reveals the Regulation of TGFβ, Pentose Phosphate and Antioxidant Defense System by Placental Growth Factor in Retinal Endothelial Cell Functions: Implication in Diabetic Retinopathy

Version 1 : Received: 9 July 2019 / Approved: 10 July 2019 / Online: 10 July 2019 (07:48:20 CEST)

How to cite: Huang, H.; Saddala, M.S.; Lennikov, A.; Mukwaya, A.; Fan, L. Pathway-Focused Gene Interaction Analysis Reveals the Regulation of TGFβ, Pentose Phosphate and Antioxidant Defense System by Placental Growth Factor in Retinal Endothelial Cell Functions: Implication in Diabetic Retinopathy. Preprints 2019, 2019070140 (doi: 10.20944/preprints201907.0140.v1). Huang, H.; Saddala, M.S.; Lennikov, A.; Mukwaya, A.; Fan, L. Pathway-Focused Gene Interaction Analysis Reveals the Regulation of TGFβ, Pentose Phosphate and Antioxidant Defense System by Placental Growth Factor in Retinal Endothelial Cell Functions: Implication in Diabetic Retinopathy. Preprints 2019, 2019070140 (doi: 10.20944/preprints201907.0140.v1).

Abstract

Placental growth factor (PlGF or PGF) is a member of the VEGF family, which is known to play a critical role in pathological angiogenesis, inflammation, and endothelial cell barrier function. However, the molecular mechanisms by which PlGF mediates its effects in non-proliferative diabetic retinopathy (DR) remain elusive. In this study, we performed transcriptome-wide profiling of differential gene expression for human retinal endothelial cells (HRECs) treated with PlGF antibody. The effect of antibody treatment on the samples was validated using trans-endothelial electric resistance (TEER), and western blot. A total of 3760 genes (1750 upregulated and 2010 downregulated) were found to be differentially expressed between the control and PlGF antibody treatment group. These differentially expressed genes (DEGs) were used for gene ontology and enrichment analysis to identify gene function, signal pathway, and interaction networks. The gene ontology results revealed that catalytic activity (GO:0003824) of molecular function, cell (GO:0005623) of the cellular component, and cellular process (GO:0009987) were among the most enriched biological processes. Pathways such as TGF-β, VEGF-VEGFR2, p53, apoptosis, pentose phosphate pathway, and ubiquitin-proteasome pathway, were among the most enriched, and TGF-β1 was identified as a primary upstream regulator. These data provide new insights into the underlying molecular mechanisms of PlGF in mediating biological functions, in relation to DR.

Subject Areas

PlGF; PGF; blood-retinal barrier; RNA Seq; HREC; gene ontology; fastQC; Trimmomatic; KEGG; pentose phosphate pathway; TGF-β

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