Important Metabolites in Maintaining Folate Cycle, Homocysteine, and Polyamine Metabolism Associated with Ranibizumab Treatment in Cultured Human Tenon’s Fibroblasts
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 h...
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| Формат: | Статья |
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MDPI
2019
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| _version_ | 1825722132683816960 |
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| author | Md Noh, Siti Munirah Sheikh Abdul Kadir, Siti Hamimah Vasudevan, Sushil |
| author_facet | Md Noh, Siti Munirah Sheikh Abdul Kadir, Siti Hamimah Vasudevan, Sushil |
| author_sort | Md Noh, Siti Munirah |
| collection | UM |
| description | 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. |
| first_indexed | 2024-03-06T06:00:59Z |
| format | Article |
| id | um.eprints-23822 |
| institution | Universiti Malaya |
| last_indexed | 2024-03-06T06:00:59Z |
| publishDate | 2019 |
| publisher | MDPI |
| record_format | dspace |
| spelling | um.eprints-238222020-02-18T01:59:57Z http://eprints.um.edu.my/23822/ Important Metabolites in Maintaining Folate Cycle, Homocysteine, and Polyamine Metabolism Associated with Ranibizumab Treatment in Cultured Human Tenon’s Fibroblasts Md Noh, Siti Munirah Sheikh Abdul Kadir, Siti Hamimah Vasudevan, Sushil R Medicine 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. MDPI 2019 Article PeerReviewed 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 <https://doi.org/10.3390/biom9060243>. https://doi.org/10.3390/biom9060243 doi:10.3390/biom9060243 |
| spellingShingle | R Medicine Md Noh, Siti Munirah Sheikh Abdul Kadir, Siti Hamimah Vasudevan, Sushil Important Metabolites in Maintaining Folate Cycle, Homocysteine, and Polyamine Metabolism Associated with Ranibizumab Treatment in Cultured Human Tenon’s Fibroblasts |
| title | Important Metabolites in Maintaining Folate Cycle, Homocysteine, and Polyamine Metabolism Associated with Ranibizumab Treatment in Cultured Human Tenon’s Fibroblasts |
| title_full | Important Metabolites in Maintaining Folate Cycle, Homocysteine, and Polyamine Metabolism Associated with Ranibizumab Treatment in Cultured Human Tenon’s Fibroblasts |
| title_fullStr | Important Metabolites in Maintaining Folate Cycle, Homocysteine, and Polyamine Metabolism Associated with Ranibizumab Treatment in Cultured Human Tenon’s Fibroblasts |
| title_full_unstemmed | Important Metabolites in Maintaining Folate Cycle, Homocysteine, and Polyamine Metabolism Associated with Ranibizumab Treatment in Cultured Human Tenon’s Fibroblasts |
| title_short | Important Metabolites in Maintaining Folate Cycle, Homocysteine, and Polyamine Metabolism Associated with Ranibizumab Treatment in Cultured Human Tenon’s Fibroblasts |
| title_sort | important metabolites in maintaining folate cycle homocysteine and polyamine metabolism associated with ranibizumab treatment in cultured human tenon s fibroblasts |
| topic | R Medicine |
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