PloS one · 2025
Effect of dopamine on TGF-β2 secretion by human retinal pigment epithelial cells and the underlying mechanism.
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Fan Jing, Zhang Qiujin, Zheng Liu, Yang Binbin, Jin He, Meng Tingyu, Ding Zhixiang
Аннотация
BACKGROUND: Dopamine is known to play a role in the development of myopia. In this study, we investigated the effect of dopamine (DA) on the secretion of transforming growth factor-β2 (TGF-β2) in human retinal pigment epithelial (RPE) cells. Additionally, we examined the effects of SCH23390 (D1 receptor antagonist) and sulpiride (D2 receptor antagonist) on TGF-β2 levels in ARPE-19 cells to elucidate the underlying mechanism of DA in myopia development.
METHODS: Human RPE cells were cultured with or without different concentrations of DA, SCH23390, or sulpiride. Cell proliferation was examined using the CCK-8 assay. Cell migration was assessed by performing a cell scratch (wound healing) assay. The expression of TGF-β2 was evaluated at the mRNA and protein levels by real-time PCR and western blotting, respectively. Furthermore, the secretion of TGF-β2 into the ARPE-19 cell supernatant was quantified using ELISA.
RESULTS: Treatment with 20 μg/mL of DA significantly increased (P < 0.05) the mRNA and protein expression levels of DRD1, DRD2, YAP, and TEAD and decreased TGF-β2 levels compared with that in control group. However, treatment with 24 μg/mL of SCH23390 for 24 h significantly decreased (P < 0.05) DRD1 and TGF-β2 mRNA expression and increased DRD2, YAP, and TEAD mRNA expression in ARPE-19 cells compared with that in the control group. Additionally, the protein expression levels of TGF-β2, YAP, TEAD, and SMAD7 were consistent with the mRNA levels. Notably, treatment with sulpiride (14 μg/mL) increased (P < 0.05) DRD1 and TGF-β2 expression and decreased DRD2, YAP, and TEAD expression in the cells at both the mRNA and protein levels compared with that in the control group.
CONCLUSIONS: Our findings suggest that dopamine suppresses TGF-β2 secretion in human retinal pigment epithelial cells primarily through activation of D2 receptors, which appears to involve the YAP-TGF-β-Smad signaling pathway. This regulatory mechanism may contribute to the control of scleral remodeling and thus influence the development of myopia.
METHODS: Human RPE cells were cultured with or without different concentrations of DA, SCH23390, or sulpiride. Cell proliferation was examined using the CCK-8 assay. Cell migration was assessed by performing a cell scratch (wound healing) assay. The expression of TGF-β2 was evaluated at the mRNA and protein levels by real-time PCR and western blotting, respectively. Furthermore, the secretion of TGF-β2 into the ARPE-19 cell supernatant was quantified using ELISA.
RESULTS: Treatment with 20 μg/mL of DA significantly increased (P < 0.05) the mRNA and protein expression levels of DRD1, DRD2, YAP, and TEAD and decreased TGF-β2 levels compared with that in control group. However, treatment with 24 μg/mL of SCH23390 for 24 h significantly decreased (P < 0.05) DRD1 and TGF-β2 mRNA expression and increased DRD2, YAP, and TEAD mRNA expression in ARPE-19 cells compared with that in the control group. Additionally, the protein expression levels of TGF-β2, YAP, TEAD, and SMAD7 were consistent with the mRNA levels. Notably, treatment with sulpiride (14 μg/mL) increased (P < 0.05) DRD1 and TGF-β2 expression and decreased DRD2, YAP, and TEAD expression in the cells at both the mRNA and protein levels compared with that in the control group.
CONCLUSIONS: Our findings suggest that dopamine suppresses TGF-β2 secretion in human retinal pigment epithelial cells primarily through activation of D2 receptors, which appears to involve the YAP-TGF-β-Smad signaling pathway. This regulatory mechanism may contribute to the control of scleral remodeling and thus influence the development of myopia.