Md Noh, Siti Munirah and Sheikh Abdul Kadir, Siti Hamimah and Vasudevan, Sushil (2019) Important Metabolites in Maintaining Folate Cycle, Homocysteine, and Polyamine Metabolism Associated with Ranibizumab Treatment in Cultured Human Tenon’s Fibroblasts. Biomolecules, 9 (6). p. 243. ISSN 2218-273X, DOI https://doi.org/10.3390/biom9060243.
Full text not available from this repository.Abstract
The anti-fibrotic properties of ranibizumab have been well documented. As an antagonist to vascular endothelial growth factor (VEGF), ranibizumab works by binding and neutralizing all active VEGF-A, thus limiting progressive cell growth and proliferation. Ranibizumab application in ocular diseases has shown remarkable desired effects; however, to date, its antifibrotic mechanism is not well understood. In this study, we identified metabolic changes in ranibizumab-treated human Tenon’s fibroblasts (HTFs). Cultured HTFs were treated for 48 h 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 analyzed using Agilent Mass Hunter Qualitative Analysis software to identify the most regulated metabolite following ranibizumab treatment. At p-value < 0.01 with the cut off value of two-fold change, 31 identified metabolites were found to be significantly upregulated in ranibizumab-treated group, with six of the mostly upregulated having insignificant role in fibroblast cell cycle and wound healing regulations. Meanwhile, 121 identified metabolites that were downregulated, and seven of the mostly downregulated are significantly involved in cell cycle and proliferation. Our findings suggest that ranibizumab abrogates the tissue scarring and wound healing process by regulating the expression of metabolites associated with fibrotic activity. In particular, we found that vitamin Bs are important in maintaining normal folate cycle, nucleotide synthesis, and homocysteine and spermidine metabolism. This study provides an insight into ranibizumab’s mechanism of action in HTFs from the perspective of metabolomics. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
| Item Type: | Article |
|---|---|
| Funders: | RAGS Grant, 600-RMI/RAGS 5/3(98/2012), Ministry of Science, Technology and Innovation (MOSTI), 100-RMI/SF 16/6/2, University of Malaya and Universiti Teknologi MARA (UiTM) |
| Uncontrolled Keywords: | anti-VEGF; ranibizumab; trabeculectomy |
| Subjects: | R Medicine |
| Divisions: | UM Centre Innovation and Commercialization |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 18 Feb 2020 01:59 |
| Last Modified: | 18 Feb 2020 01:59 |
| URI: | http://eprints.um.edu.my/id/eprint/23822 |
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