Loss of TRPV4 Cation Channel Inhibition of Macrophage Infiltration and Neovascularization in a Mouse Cornea.
Takayoshi SumiokaHiroki IwanishiShingo YasudaKana IchikawaMasayasu MiyazimaMasahide KokadoYuka OkadaShizuya SaikaPublished in: Laboratory investigation; a journal of technical methods and pathology (2023)
Corneal injury-associated inflammation could induce inward-growing neovascularization from the periphery of the tissue. Such neovascularization could cause stromal opacification and curvature disturbance, and both potentially impair visual function. In this study, we determined the effects of the loss of transient receptor potential vanilloid 4 (TRPV4) expression on the development of neovascularization in the corneal stroma in mice by producing a cauterization injury in the central area of the cornea. New vessels were immunohistochemically labeled with anti-TRPV4 antibodies. TRPV4 gene knockout suppressed the growth of such CD31-labeled neovascularization in association with the suppression of infiltration of macrophages and tissue messenger RNA expression of the vascular endothelial cell growth factor A level. Treatment of cultured vascular endothelial cells with supplementation of HC-067047 (0.1 μM, 1 μM, or 10 μM), a TRPV4 antagonist, attenuated the formation of a tube-like structure with sulforaphane (15 μM, for positive control) that modeled the new vessel formation. Therefore, the TRPV4 signal is involved in injury-induced macrophagic inflammation and neovascularization activity by vascular endothelial cells in a mouse corneal stroma. TRPV4 could be a therapeutic target to prevent unfavorable postinjury neovascularization in the cornea.
Keyphrases
- endothelial cells
- vascular endothelial growth factor
- diabetic retinopathy
- high glucose
- neuropathic pain
- growth factor
- poor prognosis
- optical coherence tomography
- oxidative stress
- spinal cord injury
- binding protein
- type diabetes
- spinal cord
- gene expression
- long non coding rna
- adipose tissue
- pet imaging
- copy number
- human health
- transcription factor
- stress induced
- replacement therapy
- cataract surgery