Protective Effect of NO 2 -OA on Oxidative Stress, Gliosis, and Pro-Angiogenic Response in Müller Glial Cells.
Cells(2023)
摘要
Inflammation and oxidative and nitrosative stress are involved in the pathogenesis of proliferative retinopathies (PR). In PR, a loss of balance between pro-angiogenic and anti-angiogenic factors favors the secretion of vascular endothelial growth factor (VEGF). This vascular change results in alterations in the blood-retinal barrier, with extravasation of plasma proteins such as α-macroglobulin (αM) and gliosis in Müller glial cells (MGCs, such as MIO-M1). It is well known that MGCs play important roles in healthy and sick retinas, including in PR. Nitro-fatty acids are electrophilic lipid mediators with anti-inflammatory and cytoprotective properties. Our aim was to investigate whether nitro-oleic acid (NO-OA) is beneficial against oxidative stress, gliosis, and the pro-angiogenic response in MGCs. Pure synthetic NO-OA increased HO-1 expression in a time- and concentration-dependent manner, which was abrogated by the Nrf2 inhibitor trigonelline. In response to phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS), NO-OA prevented the ROS increase and reduced the gliosis induced by αM. Finally, when hypoxic MGCs were incubated with NO-OA, the increase in VEGF mRNA expression was not affected, but under hypoxia and inflammation (IL-1β), NO-OA significantly reduced VEGF mRNA levels. Furthermore, NO-OA inhibited endothelial cell (BAEC) tubulogenesis. Our results highlight NO-OA's protective effect on oxidative damage, gliosis; and the exacerbated pro-angiogenic response in MGCs.
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关键词
Müller glial cells,Nrf2-Keap1 antioxidant pathway,gliosis,nitro-oleic acids,pro-angiogenic factor,reactive oxygen species
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