Important metabolites in maintaining folic acid, homocysteine and polyamine metabolism associated with ranibizumab treatment in cultured Human Tenon’s Fibroblast

Faculty of Medicine, University Teknologi MARA (UiTM), Sungai Buluh Campus, Sungai Buloh, Selangor, Malaysia
University of Malaya Centre for Innovation and Commercialization (UMCIC), University of Malaya, Kuala Lumpur, Kuala Lumpur, Malaysia
DOI
10.7287/peerj.preprints.27492v1
Subject Areas
Molecular Biology, Ophthalmology
Keywords
Anti-VEGF, Ranibizumab, Metabolomic Analysis, Folic Acid Cycle, Homocystein Metabolism, Polyamine Metabolism, Wound Healing
Copyright
© 2019 Md Noh et al.
Licence
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
Cite this article
Md Noh SM, Sheikh Abdul Kadir SH, Vasudevan SK. 2019. Important metabolites in maintaining folic acid, homocysteine and polyamine metabolism associated with ranibizumab treatment in cultured Human Tenon’s Fibroblast. PeerJ Preprints 7:e27492v1

Abstract

Anti-fibrotic properties of ranibizumab have been well documented. As an antagonist to Vascular Endothelial Growth Factor (VEGF), ranibizumab works by binding and neutralizes all active VEGF, thus limits the progressive cell growth and proliferation. Its application in ocular diseases has shown remarkable desired effects, however to date its anti-fibrotic mechanism is not well understood. In this study, we identified metabolic changes in ranibizumab-treated Human Tenos’s fibroblast (HTF). Cultured HTFs were treated for48 hours with 0.5 mg/ml of ranibizumab and 0.5 mg/ml control IgG antibody which serves as a negative control. Samples from each group were injected into Agilent 6520 Q-TOF Liquid Chromatography/ Mass Spectrometer (LC/MS) System to establish the metabolite expression in both ranibizumab treated cells and control group. Data obtained was analysed using Agilent Mass Hunter Qualitative Analysis software to identify the most regulated metabolite following ranibizumab treatment. At statistical analysis of p-value < 0.01 with the cut off value of two-fold change, 31 identified metabolites were found to be significantly up-regulated in ranibizumab-treated group, with 6 of the mostly up-regulated have insignificant role in fibroblast’s cell cycle and wound healing regulations Meanwhile, 121 identified metabolites were down-regulated with seven of the mostly down-regulated are significantly involved in cell cycle and proliferation. Our findings demonstrated that ranibizumab abrogates the tissue scarring process and wound healing formation by regulating the expression of metabolites associated with fibrotic activity. In particular, we found that vitamin Bs are important in maintaining normal folic acid cycle, nucleotide synthesis, homocysteine and spermidine metabolism. This study provides an insight of ranibizumab mechanism of actions on HTFs from the perspective of metabolomics.

Author Comment

This is a submission to PeerJ for review.

Supplemental Information

Up-regulated and down-regulated metabolite in ranibizumab treated-HTFs group and control HTFs group

DOI: 10.7287/peerj.preprints.27492v1/supp-1