Abstract
BackgroundBy investigating that (i) all-trans retinoic acid (ATRA) affects human retinal pigment epithelium (RPE) in expressing and secreting transforming growth factor (TGF)-β2 and (ii) U73122 (phospholipase C inhibitor) and SQ22536 (adenylyl cyclase inhibitor) regulate the ATRA-induced secretion of TGF-β2 in human RPE, we sought to interpret the signaling pathway of ATRA in promoting the development of myopia.MethodsThe RPE cell line (D407) was treated with (i) ATRA (10 μM), (ii) U73122 (5–40 μM) and ATRA (10 μM), or (iii) SQ22536 (5–40 μM) and ATRA (10 μM). The control group was no-treated. After stimulated at 2, 4, 8, 16, 24, and 48 h, The expression and secretion of TGF-β2 was detected.ResultsTGF-β2 in the cytoplasm was time-dependent increased by ATRA (p < 0.001). A time-dependent increase in the TGF-β2 protein of the supernatant was induced by ATRA (p < 0.001). U73122 (in the range of 5 to 40 μM) could suppress the secretion of TGF-β2 induced by ATRA (p < 0.001), and 40 μM U73122 could completely inhibit the up-regulated effect of 10 μM ATRA. However, SQ22536 (in the range of 5 to 40 μM) had no impact on the secretion of TGF-β2 induced by ATRA (p > 0.05).ConclusionsIn RPE cells, ATRA stimulates the secretion of TGF-β2 via the phospholipase C signaling pathway but not the adenylyl cyclase signaling pathway. U73122 may inhibit the promotion of ATRA in the development of myopia.
Highlights
By investigating that (i) all-trans retinoic acid (ATRA) affects human retinal pigment epithelium (RPE) in expressing and secreting transforming growth factor (TGF)-β2 and (ii) U73122 and SQ22536 regulate the ATRA-induced secretion of TGF-β2 in human RPE, we sought to interpret the signaling pathway of ATRA in promoting the development of myopia
To identify whether ATRA can stimulate D407 cells in expressing and secreting TGF-β2, we examined the concentration of TGF-β2 in the cytoplasm, and the level of TGF-β2 secreted in the supernatant in the ATRA treatment group and control group at 2, 4, 8, 16, 24 and 48 h
These results proved that ATRA could induce the significant up-regulation of TGF-β2 in both cytoplasm and supernatant in a time-dependent manner
Summary
By investigating that (i) all-trans retinoic acid (ATRA) affects human retinal pigment epithelium (RPE) in expressing and secreting transforming growth factor (TGF)-β2 and (ii) U73122 (phospholipase C inhibitor) and SQ22536 (adenylyl cyclase inhibitor) regulate the ATRA-induced secretion of TGF-β2 in human RPE, we sought to interpret the signaling pathway of ATRA in promoting the development of myopia. Previous studies have reported that all-trans retinoic acid (ATRA) can up-regulate the expression of tight junction-associated protein in the retinal pigment epithelium (RPE)-choroid complex and promotes the epithelial barrier function of the RPE monolayer during the development of myopia [9, 10]. All of these results indicate that RPE plays an important role in the retinal RA signal controlling the scleral remodeling of myopia.
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