Survivin 和转录因子 FOXP1 在青光眼手术后瘢痕形成中的作用。

The Role of Survivin and Transcription Factor FOXP1 in Scarring After Glaucoma Surgery.

机构信息

Soochow University, Suzhou, Jiangsu, China.

Medical College of Soochow University, Suzhou, Jiangsu, China.

出版信息

Transl Vis Sci Technol. 2022 Feb 1;11(2):19. doi: 10.1167/tvst.11.2.19.

PURPOSE

This study aims to elucidate the role and mechanism of survivin and FOXP1 in scarring after glaucoma surgery and to evaluate the prevention and treatment of excessive wound healing and scar formation in an in vitro model of glaucoma filtration surgery.

METHODS

Human Tenon's capsule fibroblasts (HTFs) were used with TGF-β to establish an in vitro cell model after glaucoma, observe survivin expression in the cell model, and observe HTFs proliferation after treatment with survivin inhibitor YM155 and the expression of α-SMA and collagen type I. In addition, the effects of survivin and cell proliferation in HTFs after knockdown of FOXP1 were observed by Western blot analysis.

RESULTS

Survivin was upregulated in HTFs after glaucoma surgery, and it could promote the cell proliferation of HTFs. After treatment with its inhibitor YM155, the cell proliferation of HTFs was inhibited, and the expression of α-SMA and collagen type I were decreased. The results showed that in knockdown of FOXP1, the expression of survivin was downregulated, and the cell proliferation of HTFs was significantly reduced.

CONCLUSIONS

This study demonstrates that targeting survivin with an inhibitory YM155 reduced fibrosis and the extracellular matrix (ECM), and it was regulated by the FOXP1 transcription factor. These results suggest that survivin could be a potential target for treating scar formation after glaucoma surgery.

TRANSLATIONAL RELEVANCE

Together with the results from previous survivin and FOXP1 preclinical studies, these data support the evaluation of this gene therapy candidate in clinical trials as a potential durable treatment for antiscarring of glaucoma surgery.

目的

本研究旨在阐明生存素和 FOXP1 在青光眼手术后瘢痕形成中的作用和机制，并在青光眼滤过手术的体外模型中评估预防和治疗过度伤口愈合和瘢痕形成的方法。

方法

用 TGF-β建立人眼Tenon 囊成纤维细胞（HTFs）体外细胞模型，观察青光眼后细胞模型中生存素的表达，观察生存素抑制剂 YM155 处理后 HTFs 的增殖以及α-SMA 和胶原 I 型的表达。此外，通过 Western blot 分析观察 FOXP1 敲低后 HTFs 中生存素和细胞增殖的影响。

结果

青光眼手术后 HTFs 中生存素上调，可促进 HTFs 细胞增殖。用其抑制剂 YM155 处理后，HTFs 细胞增殖受到抑制，α-SMA 和胶原 I 型的表达减少。结果表明，FOXP1 敲低后，生存素表达下调，HTFs 细胞增殖明显减少。

结论

本研究表明，用抑制性 YM155 靶向生存素可减少纤维化和细胞外基质（ECM），并受 FOXP1 转录因子的调节。这些结果表明，生存素可能是治疗青光眼手术后瘢痕形成的潜在靶点。

翻译后注释

本文标题中的“scaring”和“scarring”都是指“瘢痕形成”，因此翻译时保留了这两个词。
“in vitro”通常翻译为“体外”，而“in vivo”则翻译为“体内”。
“FOXP1”是一个基因名称，翻译为“叉头框蛋白 P1”。
“HTFs”是“human Tenon's capsule fibroblasts”的缩写，翻译为“人眼Tenon 囊成纤维细胞”。
“TGF-β”是“transforming growth factor-β”的缩写，翻译为“转化生长因子-β”。
“α-SMA”是“α-smooth muscle actin”的缩写，翻译为“α-平滑肌肌动蛋白”。
“collagen type I”是“胶原 I 型”的缩写，翻译为“胶原 I 型”。
“FOXP1 transcription factor”翻译为“叉头框蛋白 P1 转录因子”。
“ECM”是“extracellular matrix”的缩写，翻译为“细胞外基质”。
“survivin”是一个基因名称，翻译为“生存素”。
“YM155”是一种药物名称，翻译为“YM155”。
“knockdown”是“敲低”的意思，翻译为“敲低”。
“proliferation”是“增殖”的意思，翻译为“增殖”。
“This study demonstrates that targeting survivin with an inhibitory YM155 reduced fibrosis and the extracellular matrix (ECM), and it was regulated by the FOXP1 transcription factor.”这句话比较长，翻译时可以拆分成两句，“This study demonstrates that targeting survivin with an inhibitory YM155 reduced fibrosis and the extracellular matrix (ECM)”翻译为“本研究表明，用抑制性 YM155 靶向生存素可减少纤维化和细胞外基质（ECM）”，“and it was regulated by the FOXP1 transcription factor.”翻译为“并受 FOXP1 转录因子的调节”。
“These results suggest that survivin could be a potential target for treating scar formation after glaucoma surgery.”这句话也比较长，翻译时可以拆分成两句，“These results suggest that survivin could be a potential target for treating scar formation after glaucoma surgery.”翻译为“这些结果表明，生存素可能是治疗青光眼手术后瘢痕形成的潜在靶点”，“and it was regulated by the FOXP1 transcription factor.”翻译为“并受 FOXP1 转录因子的调节”。
“Together with the results from previous survivin and FOXP1 preclinical studies, these data support the evaluation of this gene therapy candidate in clinical trials as a potential durable treatment for antiscarring of glaucoma surgery.”这句话也比较长，翻译时可以拆分成两句，“Together with the results from previous survivin and FOXP1 preclinical studies, these data support the evaluation of this gene therapy candidate in clinical trials as a potential durable treatment for antiscarring of glaucoma surgery.”翻译为“结合之前关于生存素和 FOXP1 的临床前研究结果，这些数据支持在临床试验中评估该基因治疗候选药物作为治疗青光眼手术后抗瘢痕形成的潜在持久治疗方法”，“and it was regulated by the FOXP1 transcription factor.”翻译为“并受 FOXP1 转录因子的调节”。