4.3 Article

Suppression of transient receptor potential canonical channel 4 inhibits vascular endothelial growth factor-induced retinal neovascularization

Journal

CELL CALCIUM
Volume 57, Issue 2, Pages 101-108

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.ceca.2015.01.002

Keywords

Canonical transient receptor potential 4 channel; Oxygen-induced retinopathy; Retinal neovascularization; Vascular endothelial growth factor

Categories

Funding

  1. Seoul National University Research Grant [800-20140542]
  2. Seoul National University Hospital Research Fund [03-2014-0260]
  3. Pioneer Research Program of NRF/MEST [2012-0009544]
  4. Bio-Signal Analysis Technology Innovation Program of NRF/MEST [2009-0090895]
  5. National Research Foundation of Korea [2009-0090895] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and thus contributes to many vasoproliferative retinopathies including retinopathy of prematurity. Based on the importance of canonical transient receptor potential (TRPC) channels in VEGF signaling, we firstly evaluated the expression of TRPC channels in mouse retina by reverse transcriptase-polymerase chain reaction. All seven TRPC channels were expressed in mouse retina. TRPC4 channels were chosen for further analysis based on their upregulation on hypoxic retina according to the GEO database under the identifier GSE19886. Interestingly, TRPC4 suppression by intravitreal injection of siRNA against mTRPC4 significantly inhibited retinal neovascularization. To further investigate the effect of TRPC4 suppression on neovascularization, human retina microvascular endothelial cells (HRMECs) that are responsible for initiating neovascularization in response to increased VEGF in OIR retina were transfected with siRNA against TRPC4. As we have expected, suppression of TRPC4 effectively inhibited VEGF-induced migration and tube formation as well. Further evaluation on VEGF signaling pathway by western blot analysis of signaling molecules discovered that VEGF-induced activation of ERK, p38 MAPK and AKT signaling pathways were inhibited by suppression of TRPC4. These findings suggest that suppression of TRPC4 could be an alternative therapeutic option for VEGF-induced retinal neovascularization. (C) 2015 Elsevier Ltd. All rights reserved.

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