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Toll-Like Receptor Signalling Pathways Regulate Hypoxic Stress Induced Fibroblast Growth Factor but Not Vascular Endothelial Growth Factor-A in Human Microvascular Endothelial Cells

Academic Ophthalmology, School of Medicine, Queens Medical Centre, University of Nottingham, Eye & ENT Building, B Floor, Derby Road, Nottingham NG7 2UH, UK
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Academic Editor: Pier Paolo Claudio
Int. J. Transl. Med. 2021, 1(1), 25-38; https://0-doi-org.brum.beds.ac.uk/10.3390/ijtm1010003
Received: 30 March 2021 / Revised: 11 May 2021 / Accepted: 12 May 2021 / Published: 27 May 2021
(This article belongs to the Special Issue Diabetic Retinopathy)
Retinal diseases are the leading causes of irreversible blindness worldwide. The role of toll-like receptor (TLR) signalling mechanisms (MyD88 and TRIF) in the production of pro-angiogenic growth factors from human microvascular endothelial cells (HMEC-1) under hypoxic stress remains unexplored. HMEC-1 was incubated under normoxic (5% CO2 at 37 °C) and hypoxic (1% O2, 5% CO2, and 94% N2; at 37 °C) conditions for 2, 6, 24, and 48 h, respectively. For TLR pathway analysis, HMEC-1 was pre-treated with pharmacological inhibitors (Pepinh-MyD88 and Pepinh-TRIF) and subjected to normoxia and hypoxia conditions. Gene and protein expressions of vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor (FGF-2), hypoxia inducible factor 1-alpha (HIF1-α) were performed using quantitative polymerase chain reaction (qPCR), ELISA, and Western blot methodologies. Levels of TLR3 and TLR4 were analysed by flow cytometry. Under hypoxia, levels of VEGF-A and FGF-2 were elevated in a time-dependent fashion. Inhibition of MyD88 and TRIF signalling pathways decreased FGF-2 levels but failed to modulate the secretion of VEGF-A from HMEC-1. Blocking a known regulator, endothelin receptor (ETR), also had no effect on VEGF-A secretion from HMEC-1. Overall, this study provides the proof-of-concept to target TLR signalling pathways for the management of blinding retinal diseases. View Full-Text
Keywords: retinal diseases; blindness; toll-like receptor; vascular endothelial cells; angiogenesis; VEGF; FGF; ischemia; hypoxia retinal diseases; blindness; toll-like receptor; vascular endothelial cells; angiogenesis; VEGF; FGF; ischemia; hypoxia
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MDPI and ACS Style

Akhtar, R.; Tahir, H.; Stewart, E.; Wei, R.; Mohammed, I.; Amoaku, W.M. Toll-Like Receptor Signalling Pathways Regulate Hypoxic Stress Induced Fibroblast Growth Factor but Not Vascular Endothelial Growth Factor-A in Human Microvascular Endothelial Cells. Int. J. Transl. Med. 2021, 1, 25-38. https://0-doi-org.brum.beds.ac.uk/10.3390/ijtm1010003

AMA Style

Akhtar R, Tahir H, Stewart E, Wei R, Mohammed I, Amoaku WM. Toll-Like Receptor Signalling Pathways Regulate Hypoxic Stress Induced Fibroblast Growth Factor but Not Vascular Endothelial Growth Factor-A in Human Microvascular Endothelial Cells. International Journal of Translational Medicine. 2021; 1(1):25-38. https://0-doi-org.brum.beds.ac.uk/10.3390/ijtm1010003

Chicago/Turabian Style

Akhtar, Rukhsar, Husain Tahir, Elizabeth Stewart, Ruoxin Wei, Imran Mohammed, and Winfried M. Amoaku 2021. "Toll-Like Receptor Signalling Pathways Regulate Hypoxic Stress Induced Fibroblast Growth Factor but Not Vascular Endothelial Growth Factor-A in Human Microvascular Endothelial Cells" International Journal of Translational Medicine 1, no. 1: 25-38. https://0-doi-org.brum.beds.ac.uk/10.3390/ijtm1010003

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