All-trans retinoic acid stimulates the secretion of TGF-β2 via the phospholipase C but not the adenylyl cyclase signaling pathway in retinal pigment epithelium cells

BACKGROUND: By investigating that (i) all-trans retinoic acid (ATRA) affects human retinal pigment epithelium (RPE) in expressing and secreting transforming growth factor (TGF)-β(2) and (ii) U73122 (phospholipase C inhibitor) and SQ22536 (adenylyl cyclase inhibitor) regulate the ATRA-induced secretion of TGF-β(2) in human RPE, we sought to interpret the signaling pathway of ATRA in promoting the development of myopia. METHODS: The 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-β(2) was detected. RESULTS: TGF-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-β(2) induced by ATRA (p > 0.05). CONCLUSIONS: In RPE cells, ATRA stimulates the secretion of TGF-β(2) 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.