June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
The vicious cycle of TGF-β autoinduction contributes to VEGF-A expression in Müller glial cells
Author Affiliations & Notes
  • Di Wu
    Laboratory of Ocular Cell Biology & Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  • Atsuhiro Kanda
    Laboratory of Ocular Cell Biology & Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  • Miyuki Murata
    Laboratory of Ocular Cell Biology & Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  • Susumu Ishida
    Laboratory of Ocular Cell Biology & Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  • Footnotes
    Commercial Relationships   Di Wu, None; Atsuhiro Kanda, None; Miyuki Murata, None; Susumu Ishida, None
  • Footnotes
    Support  MEXT KAKENHI Grant 19K09944
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 694. doi:
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      Di Wu, Atsuhiro Kanda, Miyuki Murata, Susumu Ishida; The vicious cycle of TGF-β autoinduction contributes to VEGF-A expression in Müller glial cells. Invest. Ophthalmol. Vis. Sci. 2020;61(7):694.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Müller glia is one of the sources of vascular endothelial growth factor (VEGF)-A, a major angiogenic factor that contributes to the pathogenesis of ocular diseases such as diabetic retinopathy. The purpose of this study was to investigate the molecular mechanism of VEGF-A production in Müller glial cells.

Methods : Immunoblot, enzyme-linked immunosorbent (ELISA) and real-time quantitative PCR (qPCR) analyses were performed to measure protein and mRNA expression levels of VEGF-A in human Müller glial cells (MIO-M1 cell line).

Results : Of various pro-fibrotic cytokines, administration of transforming growth factor (TGF)-β1 and -β2 to human Müller glial cells exclusively increased mRNA (fold change; TGF-β1 = 1.9, TGF-β2 = 1.9, p < 0.01) and protein (fold change; TGF-β1 = 4.3, TGF-β2 = 3.9, p < 0.01) levels of VEGF-A via real-time qPCR and ELISA analyses. Pretreatment with anti-TGF-β receptor (TβR)-neutralizing antibody reversed TGF-β1/2-induced mRNA expression of VEGFA (fold change; TGF-β1 = 0.9, TGF-β2 = 0.8, p < 0.05), while normal IgG did not show any recovery. Moreover, the upregulated VEGFA mRNA expression was significantly suppressed by signal transduction inhibitors (p < 0.05). Supporting these findings, administration of TGF-β1/2 to Müller glial cells increased the phosphorylated levels of signal transduction via immunoblot analyses. Moreover, TGF-β1 and TGF-β2 upregulated the expression of TGF-β1/2 via its own downstream pathway in an autocrine manner [(TGFB1 fold change; PBS = 1.0, TGF-β1 = 2.4, TGF-β2 = 2.1) and (TGFB2 fold change; PBS = 1.0 TGF-β1 = 1.6, TGF-β2 = 1.5, p < 0.05)].

Conclusions : Our present data demonstrated that the TGF-β-TβR axis activates its downstream signal pathways in Müller glial cells, causing VEGF-A production forming the vicious cycle of TGF-β autoinduction concurrently.

This is a 2020 ARVO Annual Meeting abstract.

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