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Keiko Kusumoto-Usui, Yuka Okada, HIroki Iwanishi, Kana Ichikawa, Takayoshi Sumioka, Masayasu Miyajima, Shizuya Saika; Roles of TRPA1 cation channel receptor signal in development of stromal neovascularization in a mouse cornea (The second report). Invest. Ophthalmol. Vis. Sci. 2018;59(9):3337. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To uncover the mechanism uderlying suppression of corenal neovascularizatin (NV) by gene deletion of transient receptor potential ankyrin receptor 1 (TRPA1) in mice. In ARVO 2015 we reported lacking signal suppressed cauterization-induced stromal NV and attenuated VEGF-dependent angiogenic responses of HUVECs on fibroblast feeder.
Real-time RT-PCR and immunohistochemistry were performed to evaluate the effects of loss of TRPA1 on expression of TRPA1 and angiogenic growth factor, and macrophage invasion in a cauterization-injury model in mice (n = 20). C57BL/6 (n = 20) served as control. Effects of supplementation of a TRPA1 agonist or its antagonist on VEGF-A-signal transduction, angiogenic behavior and cell proliferation were examined in HUVECs in vitro. Expression of angiogenic growth factors by cultured TRPA1-null macrophages was also examined.
Lacking TRPA1 gene counteracted macrophage infiltration and mRNA expression of VEGF-A and TGFβ1 in association with attenuation of NV formation in response to cauterization injury. Neither a TRPA1 agonist nor antagonist altered HUVEC’s proliferation via VEGF receptor-linked cell signaling pathway activation. TGFβ1 and VEGF expression remained unchanged in macrophages of TRPA1-null mice.
Mechanism of suppression of corneal NV by TRPA1 gene knockout could include inhibition of macrophage infiltration and resultant reduction of VEGF-A and TGFβ1 expression in the tissue. Loss of TRPA1 might not directly impact vascular endothelium but communication between endothelial cells and other neighboring cell types might be involved in the phenotype.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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