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中波紫外线辐射诱导 ARPE-19 细胞中 cortistatin 的过表达和生长抑素受体的激活。

Ultraviolet A radiation induces cortistatin overexpression and activation of somatostatin receptors in ARPE‑19 cells.

机构信息

CNR‑ICRM Institute of Chemistry of Molecular Recognition (ICRM), Institute of Biochemistry and Clinical Biochemistry, Catholic University School of Medicine, I‑00168 Rome, Italy.

Institute of Biochemistry and Clinical Biochemistry, Catholic University School of Medicine, I‑00168 Rome, Italy.

出版信息

Mol Med Rep. 2018 Apr;17(4):5538-5543. doi: 10.3892/mmr.2018.8547. Epub 2018 Feb 2.

Abstract

Long-term exposure to ultraviolet (UV) radiation is associated with pathological alterations of the retinal pigment epithelium (RPE). It has been indicated that Cortistatin (CST) and somatostatin (SST) are able to inhibit the neurodegeneration of the RPE associated with diabetic retinopathy and retinal ischemia via activation of SST receptors (SSTRs). To the best of our knowledge, the present study indicated for the first time that treatment with UV‑A (30 and 60 min) causes an increase of CST expression, rather than SST, which was linked with the upregulation of STTR3,4,5 subtype receptor gene expression levels. The study revealed that: i) SST and CST mRNA expression were both detected under basal conditions in a human retinal pigment epithelial cell line (Arpe‑19); ii) SST expression remained constant from baseline to 1 h of UV‑A treatment; iii) CST mRNA expression levels were 80 times increased compared with time 0 and after 30 min of exposition to ultraviolet irradiation; iv) SSTR1, SSTR2 mRNA and low levels of SSTR4 were expressed in basal conditions, whereas SSTR3 and SSTR5 mRNA were not detected under the same conditions; and v) only SSTR3, SSTR4 and SSTR5 were overexpressed after UV‑A treatment, although in a different way. In conclusion, the findings provide reasonable evidence to support the pathophysiological role of the CST/SST/SSTRs system in the adaptive response of the RPE exposed to UV‑A radiation.

摘要

长期暴露于紫外线 (UV) 辐射会导致视网膜色素上皮 (RPE) 的病理性改变。已经表明,Cortistatin (CST) 和生长抑素 (SST) 通过激活 SST 受体 (SSTRs),能够抑制与糖尿病视网膜病变和视网膜缺血相关的 RPE 神经退行性变。据我们所知,本研究首次表明,用 UV-A(30 和 60 分钟)处理会引起 CST 表达增加,而不是 SST,这与 STTR3、4、5 亚型受体基因表达水平的上调有关。该研究表明:i)在人视网膜色素上皮细胞系 (Arpe-19) 中,在基础条件下检测到 SST 和 CST mRNA 表达;ii)SST 表达在 UV-A 处理 1 小时内保持不变;iii)与时间 0 相比,CST mRNA 表达水平增加了 80 倍,并且在暴露于紫外线照射 30 分钟后;iv)在基础条件下表达 SSTR1、SSTR2 mRNA 和低水平的 SSTR4,而在相同条件下未检测到 SSTR3 和 SSTR5 mRNA;v)仅在 UV-A 处理后过表达 SSTR3、SSTR4 和 SSTR5,尽管方式不同。总之,这些发现为 CST/SST/SSTRs 系统在 RPE 暴露于 UV-A 辐射后的适应反应中的病理生理作用提供了合理的证据。

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