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全反式维甲酸通过磷脂酶C而非视网膜色素上皮细胞中的腺苷酸环化酶信号通路刺激转化生长因子-β2的分泌。

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.

作者信息

Zhang Daren, Deng Zhihong, Tan Jia, Liu Shuirong, Hu Shuyu, Tao Hui, Tang Renhong

机构信息

Department of Ophthalmology, The Third Xiangya Hospital, Central South, Changsha, Hunan, China.

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

BMC Ophthalmol. 2019 Jan 18;19(1):23. doi: 10.1186/s12886-018-1017-6.

DOI:10.1186/s12886-018-1017-6
PMID:30658598
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6339369/
Abstract

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 and (ii) U73122 (phospholipase C inhibitor) and SQ22536 (adenylyl cyclase inhibitor) regulate the ATRA-induced secretion of TGF-β 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 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 induced by ATRA (p > 0.05).

CONCLUSIONS

In RPE cells, ATRA stimulates the secretion of TGF-β 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.

摘要

背景

通过研究（i）全反式维甲酸（ATRA）对人视网膜色素上皮（RPE）表达和分泌转化生长因子（TGF）-β的影响，以及（ii）U73122（磷脂酶C抑制剂）和SQ22536（腺苷酸环化酶抑制剂）对ATRA诱导的人RPE中TGF-β分泌的调节作用，我们试图阐释ATRA促进近视发展的信号通路。

方法

RPE细胞系（D407）分别用（i）ATRA（10μM）、（ii）U73122（5 - 40μM）和ATRA（10μM）或（iii）SQ22536（5 - 40μM）和ATRA（10μM）处理。对照组不做处理。在2、4、8、16、24和48小时刺激后，检测TGF-β的表达和分泌。

结果

ATRA使细胞质中的TGF-β2呈时间依赖性增加（p < 0.001）。ATRA诱导上清液中TGF-β2蛋白呈时间依赖性增加（p < 0.001）。U73（5至40μM范围内）可抑制ATRA诱导的TGF-β2分泌（p < 0.001），40μM U73122可完全抑制10μM ATRA的上调作用。然而，SQ22536（5至40μM范围内）对ATRA诱导的TGF-β分泌无影响（p > 0.05）。

结论

在RPE细胞中，ATRA通过磷脂酶C信号通路而非腺苷酸环化酶信号通路刺激TGF-β的分泌。U73122可能抑制ATRA在近视发展中的促进作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fc9/6339369/f56e74c10e27/12886_2018_1017_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fc9/6339369/263303b94ec6/12886_2018_1017_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fc9/6339369/990d1f5f5144/12886_2018_1017_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fc9/6339369/e5b49ced3d2d/12886_2018_1017_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fc9/6339369/f56e74c10e27/12886_2018_1017_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fc9/6339369/263303b94ec6/12886_2018_1017_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fc9/6339369/990d1f5f5144/12886_2018_1017_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fc9/6339369/e5b49ced3d2d/12886_2018_1017_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fc9/6339369/f56e74c10e27/12886_2018_1017_Fig4_HTML.jpg

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