Dopamine receptor signaling regulates fibrotic activation of retinal pigmented epithelial cells.
Dopamine receptor signaling regulates fibrotic activation of retinal pigmented epithelial cells.
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多巴胺受体信号传导调节视网膜色素上皮细胞的纤维化活化。
DOI：
10.1152/ajpcell.00468.2021
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Haak,AndrewJ
中科院分区：
文献类型：
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作者：
Gao,AshleyY;Link,PatrickA;Bakri,SophieJ;Haak,AndrewJ
视网膜色素上皮细胞（RPE）在增殖性玻璃体视网膜病变（PVR）等视网膜纤维化疾病中起重要作用。本研究的目的是阐明多巴胺受体信号在调节RPE细胞纤维化激活中的作用。在人RPE细胞系ARPE-19中检测多巴胺受体的表达、多巴胺对纤维化活性的影响以及多巴胺的产生。通过测量基因表达、迁移、增殖和纤维连接蛋白沉积，评估RPE细胞在选择性多巴胺受体激动剂和拮抗剂治疗后的纤维化激活。drd2和drd5是ARPE-19细胞中表达的主要多巴胺能受体，TGF-β刺激可增强多巴胺的自分泌释放，进一步加剧纤维化活化。最后，D2多巴胺受体拮抗剂或D5多巴胺受体激动剂可抑制原纤维化基因表达、迁移、增殖和纤维连接蛋白沉积，因此可能是治疗包括PVR在内的视网膜纤维化的有效机制。
Retinal pigmented epithelial (RPE) cells play an important role in retinal fibrotic diseases such as proliferative vitreoretinopathy (PVR). The purpose of this study was to elucidate the involvement of dopamine receptor signaling in regulating the fibrotic activation of RPE cells. Dopamine receptor expression, the effect of dopamine on fibrotic activity, and dopamine production were measured in the human RPE cell line ARPE-19. The fibrotic activation of RPE cells was evaluated in response to treatments with selective dopamine receptor agonists and antagonists by measuring gene expression, migration, proliferation, and fibronectin deposition.DRD2andDRD5are the dominant dopaminergic receptors expressed in ARPE-19 cells and TGF-β stimulation enhances the autocrine release of dopamine, which we show further exasperates fibrotic activation. Finally, treatment with D2 dopamine receptor antagonists or D5 dopamine receptor agonists inhibits profibrotic gene expression, migration, proliferation, and fibronectin deposition and thus may serve as effective mechanisms for treating retinal fibrosis including PVR.